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Weg Ongkeko
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, UC San Diego School of Medicine, San Diego, CA 92093, USA

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Journal article
Published: 23 August 2021 in Cancers
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Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level.

ACS Style

Joseph C. Tsai; Omar A. Saad; Shruti Magesh; Jingyue Xu; Abby C. Lee; Wei Tse Li; Jaideep Chakladar; Mark M. Fuster; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma. Cancers 2021, 13, 4225 .

AMA Style

Joseph C. Tsai, Omar A. Saad, Shruti Magesh, Jingyue Xu, Abby C. Lee, Wei Tse Li, Jaideep Chakladar, Mark M. Fuster, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko. Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma. Cancers. 2021; 13 (16):4225.

Chicago/Turabian Style

Joseph C. Tsai; Omar A. Saad; Shruti Magesh; Jingyue Xu; Abby C. Lee; Wei Tse Li; Jaideep Chakladar; Mark M. Fuster; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2021. "Tobacco Smoke and Electronic Cigarette Vapor Alter Enhancer RNA Expression That Can Regulate the Pathogenesis of Lung Squamous Cell Carcinoma." Cancers 13, no. 16: 4225.

Journal article
Published: 21 July 2021 in Cancers
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The intra-tumor microbiome has recently been linked to epithelial–mesenchymal transition (EMT) in a number of cancers. However, the relationship between EMT and microbes in bladder cancer has not been explored. In this study, we profiled the abundance of individual microbe species in the tumor samples of over 400 muscle invasive bladder carcinoma (MIBC) patients. We then correlated microbe abundance to the expression of EMT-associated genes and genes in the extracellular matrix (ECM), which are key players in EMT. We discovered that a variety of microbes, including E. coli, butyrate-producing bacterium SM4/1, and a species of Oscillatoria, were associated with expression of classical EMT-associated genes, including E-cadherin, vimentin, SNAI2, SNAI3, and TWIST1. We also found significant correlations between microbial abundance and the expression of genes in the ECM, specifically collagens and elastin. Lastly, we found that a large number of microbes exhibiting significant correlations to EMT are also associated with clinical prognosis and outcomes. We further determined that the microbes we profiled were likely not environmental contaminants. In conclusion, we discovered that the intra-tumoral microbiome could potentially play a significant role in the regulation of EMT in MIBC.

ACS Style

Wei Li; Anjali Iyangar; Rohan Reddy; Jaideep Chakladar; Valmik Bhargava; Kyoko Sakamoto; Weg Ongkeko; Mahadevan Rajasekaran. The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma. Cancers 2021, 13, 3649 .

AMA Style

Wei Li, Anjali Iyangar, Rohan Reddy, Jaideep Chakladar, Valmik Bhargava, Kyoko Sakamoto, Weg Ongkeko, Mahadevan Rajasekaran. The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma. Cancers. 2021; 13 (15):3649.

Chicago/Turabian Style

Wei Li; Anjali Iyangar; Rohan Reddy; Jaideep Chakladar; Valmik Bhargava; Kyoko Sakamoto; Weg Ongkeko; Mahadevan Rajasekaran. 2021. "The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma." Cancers 13, no. 15: 3649.

Journal article
Published: 29 June 2021 in Computational and Structural Biotechnology Journal
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COVID-19 has infected over 35 million people worldwide and led to over 1 million deaths. Several risk factors that increase COVID-19 severity have emerged, including age and a history of cardiovascular disease, hypertension, or kidney disease. However, a number of outstanding questions persist, including whether the above comorbidities correlate with increased mortality from COVID-19 or whether age is a significant confounding variable that accounts for the observed relationship between COVID-19 severity and other comorbidities. We conducted a systematic review and meta-analysis of studies documenting COVID-19 patients with hypertension, cardiovascular disease, cerebrovascular disease, or chronic kidney disease. We classified COVID-19 cases into severe/non-severe or deceased/surviving and calculated the odds ratio (OR) for each of the four comorbidities in these cohorts. 36 studies, comprising 22,573 patients, are included in our meta-analysis. We found that hypertension is the most prevalent comorbidity in deceased COVID-19 patients (55.4%; CI: 49.4–61.3%), followed by cardiovascular disease (30.7%; CI: 22.6–38.8%), cerebrovascular disease (13.4%; CI: 9.12–19.2%), then chronic kidney disease (9.05%; CI: 5.57–15.0%). The risk of death is also significantly higher for patients with these comorbidities, with the greatest risk factor being chronic kidney disease (OR: 8.86; CI: 5.27–14.89), followed by cardiovascular disease (OR: 6.87; CI: 5.56–8.50), hypertension (OR: 4.87; CI: 4.19–5.66), and cerebrovascular disease (OR: 4.28; CI: 2.86–6.41). These risks are significantly higher than previously reported, while correlations between comorbidities and COVID-19 severity are similar to previously reported figures. Using meta-regression analysis with age as a moderating variable, we observed that age contributes to the observed risks but does not explain them fully. In this meta-analysis, we observed that cardiovascular, cerebrovascular, and kidney-related comorbidities in COVID-19 significantly contributes to greater risk of mortality and increased disease severity. We also demonstrated that age may not be a confounder to these associations.

ACS Style

Abby C. Lee; Wei Tse Li; Lauren Apostol; Jiayan Ma; Pam R. Taub; Eric Y. Chang; Mahadevan Rajasekaran; Weg M. Ongkeko. Cardiovascular, Cerebrovascular, and Renal Co-morbidities in COVID-19 Patients: A Systematic-Review and Meta-analysis. Computational and Structural Biotechnology Journal 2021, 19, 3755 -3764.

AMA Style

Abby C. Lee, Wei Tse Li, Lauren Apostol, Jiayan Ma, Pam R. Taub, Eric Y. Chang, Mahadevan Rajasekaran, Weg M. Ongkeko. Cardiovascular, Cerebrovascular, and Renal Co-morbidities in COVID-19 Patients: A Systematic-Review and Meta-analysis. Computational and Structural Biotechnology Journal. 2021; 19 ():3755-3764.

Chicago/Turabian Style

Abby C. Lee; Wei Tse Li; Lauren Apostol; Jiayan Ma; Pam R. Taub; Eric Y. Chang; Mahadevan Rajasekaran; Weg M. Ongkeko. 2021. "Cardiovascular, Cerebrovascular, and Renal Co-morbidities in COVID-19 Patients: A Systematic-Review and Meta-analysis." Computational and Structural Biotechnology Journal 19, no. : 3755-3764.

Journal article
Published: 10 June 2021 in Cells
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The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.

ACS Style

Kypros Dereschuk; Lauren Apostol; Ishan Ranjan; Jaideep Chakladar; Wei Li; Mahadevan Rajasekaran; Eric Chang; Weg Ongkeko. Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis. Cells 2021, 10, 1452 .

AMA Style

Kypros Dereschuk, Lauren Apostol, Ishan Ranjan, Jaideep Chakladar, Wei Li, Mahadevan Rajasekaran, Eric Chang, Weg Ongkeko. Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis. Cells. 2021; 10 (6):1452.

Chicago/Turabian Style

Kypros Dereschuk; Lauren Apostol; Ishan Ranjan; Jaideep Chakladar; Wei Li; Mahadevan Rajasekaran; Eric Chang; Weg Ongkeko. 2021. "Identification of Lung and Blood Microbiota Implicated in COVID-19 Prognosis." Cells 10, no. 6: 1452.

Journal article
Published: 28 May 2021 in Viruses
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Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.

ACS Style

Abby Lee; Grant Castaneda; Wei Li; Chengyu Chen; Neil Shende; Jaideep Chakladar; Pam Taub; Eric Chang; Weg Ongkeko. COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation. Viruses 2021, 13, 1018 .

AMA Style

Abby Lee, Grant Castaneda, Wei Li, Chengyu Chen, Neil Shende, Jaideep Chakladar, Pam Taub, Eric Chang, Weg Ongkeko. COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation. Viruses. 2021; 13 (6):1018.

Chicago/Turabian Style

Abby Lee; Grant Castaneda; Wei Li; Chengyu Chen; Neil Shende; Jaideep Chakladar; Pam Taub; Eric Chang; Weg Ongkeko. 2021. "COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation." Viruses 13, no. 6: 1018.

Journal article
Published: 09 April 2021 in Computational and Structural Biotechnology Journal
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While the intratumor microbiome has become increasingly implicated in cancer development, the microbial landscape of papillary thyroid carcinoma (PTC) is essentially uninvestigated. PTC is characterized by varied prognosis between gender and cancer subtype, but the cause for gender and subtype-based dissimilarities is unclear. Women are more frequently diagnosed with PTC, while men suffer more advanced-staged PTC. In addition, tall cell variants are more aggressive than classical and follicular variants of PTC. We hypothesized that intratumor microbiome composition distinctly alters the immune landscape and predicts clinical outcome between PTC subtypes and between patient genders. Raw whole-transcriptome RNA-sequencing, Level 3 normalized mRNA expression read counts, and DNA methylation 450 k sequencing data for untreated, nonirradiated tumor, and adjacent normal tissue were downloaded from the Genomic Data Commons (GDC) legacy archive for 563 thyroid carcinoma patients. Microbe counts were extracted using Pathoscope 2.0 software. We correlated microbe abundance to clinical variables and immune-associated gene expression. Gene-set enrichment, mutation, and methylation analyses were conducted to correlate microbe abundance to characterize microbes’ roles. Overall, PTC tumor tissue significantly lacked microbes that are populated in adjacent normal tissue, which suggests presence of microbes may be critical in controlling immune cell expression and regulating immune and cancer pathways to mitigate cancer growth. In contrast, we also found that microbes distinctly abundant in tall cell and male patient cohorts were also correlated with higher mutation expression and methylation of tumor suppressors. Microbe dysbiosis in specific PTC types may explain observable differences in PTC progression and pathogenesis. These microbes provide a basis for developing specialized prebiotic and probiotic treatments for varied PTC tumors.

ACS Style

Aditi Gnanasekar; Grant Castaneda; Anjali Iyangar; Shruti Magesh; Daisy Perez; Jaideep Chakladar; Wei Tse Li; Michael Bouvet; Eric Y. Chang; Weg M. Ongkeko. The intratumor microbiome predicts prognosis across gender and subtypes in papillary thyroid carcinoma. Computational and Structural Biotechnology Journal 2021, 19, 1986 -1997.

AMA Style

Aditi Gnanasekar, Grant Castaneda, Anjali Iyangar, Shruti Magesh, Daisy Perez, Jaideep Chakladar, Wei Tse Li, Michael Bouvet, Eric Y. Chang, Weg M. Ongkeko. The intratumor microbiome predicts prognosis across gender and subtypes in papillary thyroid carcinoma. Computational and Structural Biotechnology Journal. 2021; 19 ():1986-1997.

Chicago/Turabian Style

Aditi Gnanasekar; Grant Castaneda; Anjali Iyangar; Shruti Magesh; Daisy Perez; Jaideep Chakladar; Wei Tse Li; Michael Bouvet; Eric Y. Chang; Weg M. Ongkeko. 2021. "The intratumor microbiome predicts prognosis across gender and subtypes in papillary thyroid carcinoma." Computational and Structural Biotechnology Journal 19, no. : 1986-1997.

Journal article
Published: 16 November 2020 in International Journal of Molecular Sciences
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Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.

ACS Style

Joseph C. Tsai; Grant Casteneda; Abby Lee; Kypros Dereschuk; Wei Tse Li; Jaideep Chakladar; Alecio F. Lombardi; Weg M. Ongkeko; Eric Y. Chang. Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee. International Journal of Molecular Sciences 2020, 21, 8618 .

AMA Style

Joseph C. Tsai, Grant Casteneda, Abby Lee, Kypros Dereschuk, Wei Tse Li, Jaideep Chakladar, Alecio F. Lombardi, Weg M. Ongkeko, Eric Y. Chang. Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee. International Journal of Molecular Sciences. 2020; 21 (22):8618.

Chicago/Turabian Style

Joseph C. Tsai; Grant Casteneda; Abby Lee; Kypros Dereschuk; Wei Tse Li; Jaideep Chakladar; Alecio F. Lombardi; Weg M. Ongkeko; Eric Y. Chang. 2020. "Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee." International Journal of Molecular Sciences 21, no. 22: 8618.

Review
Published: 29 September 2020 in BMC Medical Informatics and Decision Making
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Background The recent Coronavirus Disease 2019 (COVID-19) pandemic has placed severe stress on healthcare systems worldwide, which is amplified by the critical shortage of COVID-19 tests. Methods In this study, we propose to generate a more accurate diagnosis model of COVID-19 based on patient symptoms and routine test results by applying machine learning to reanalyzing COVID-19 data from 151 published studies. We aim to investigate correlations between clinical variables, cluster COVID-19 patients into subtypes, and generate a computational classification model for discriminating between COVID-19 patients and influenza patients based on clinical variables alone. Results We discovered several novel associations between clinical variables, including correlations between being male and having higher levels of serum lymphocytes and neutrophils. We found that COVID-19 patients could be clustered into subtypes based on serum levels of immune cells, gender, and reported symptoms. Finally, we trained an XGBoost model to achieve a sensitivity of 92.5% and a specificity of 97.9% in discriminating COVID-19 patients from influenza patients. Conclusions We demonstrated that computational methods trained on large clinical datasets could yield ever more accurate COVID-19 diagnostic models to mitigate the impact of lack of testing. We also presented previously unknown COVID-19 clinical variable correlations and clinical subgroups.

ACS Style

Wei Tse Li; Jiayan Ma; Neil Shende; Grant Castaneda; Jaideep Chakladar; Joseph C. Tsai; Lauren Apostol; Christine O. Honda; Jingyue Xu; Lindsay M. Wong; Tianyi Zhang; Abby Lee; Aditi Gnanasekar; Thomas K. Honda; Selena Z. Kuo; Michael Andrew Yu; Eric Y. Chang; Mahadevan “ Raj” Rajasekaran; Weg M. Ongkeko. Using machine learning of clinical data to diagnose COVID-19: a systematic review and meta-analysis. BMC Medical Informatics and Decision Making 2020, 20, 1 -13.

AMA Style

Wei Tse Li, Jiayan Ma, Neil Shende, Grant Castaneda, Jaideep Chakladar, Joseph C. Tsai, Lauren Apostol, Christine O. Honda, Jingyue Xu, Lindsay M. Wong, Tianyi Zhang, Abby Lee, Aditi Gnanasekar, Thomas K. Honda, Selena Z. Kuo, Michael Andrew Yu, Eric Y. Chang, Mahadevan “ Raj” Rajasekaran, Weg M. Ongkeko. Using machine learning of clinical data to diagnose COVID-19: a systematic review and meta-analysis. BMC Medical Informatics and Decision Making. 2020; 20 (1):1-13.

Chicago/Turabian Style

Wei Tse Li; Jiayan Ma; Neil Shende; Grant Castaneda; Jaideep Chakladar; Joseph C. Tsai; Lauren Apostol; Christine O. Honda; Jingyue Xu; Lindsay M. Wong; Tianyi Zhang; Abby Lee; Aditi Gnanasekar; Thomas K. Honda; Selena Z. Kuo; Michael Andrew Yu; Eric Y. Chang; Mahadevan “ Raj” Rajasekaran; Weg M. Ongkeko. 2020. "Using machine learning of clinical data to diagnose COVID-19: a systematic review and meta-analysis." BMC Medical Informatics and Decision Making 20, no. 1: 1-13.

Journal article
Published: 18 September 2020 in Cancers
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An intra-pancreatic microbiota was recently discovered in several prominent studies. Since pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers worldwide, and the intratumor microbiome was found to be a significant contributor to carcinogenesis in other cancers, this study aims to characterize the PAAD microbiome and elucidate how it may be associated with PAAD prognosis. We further explored the association between the intra-pancreatic microbiome and smoking and gender, which are both risk factors for PAAD. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance, which was correlated to clinical variables and to cancer and immune-associated gene expression, to determine how microbes may contribute to cancer progression. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. This is the first large-scale study to report microbiome-immune correlations in human pancreatic cancer samples. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression.

ACS Style

Jaideep Chakladar; Selena Z. Kuo; Grant Castaneda; Wei Tse Li; Aditi Gnanasekar; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. The Pancreatic Microbiome Is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers. Cancers 2020, 12, 2672 .

AMA Style

Jaideep Chakladar, Selena Z. Kuo, Grant Castaneda, Wei Tse Li, Aditi Gnanasekar, Michael Andrew Yu, Eric Y. Chang, Xiao Qi Wang, Weg M. Ongkeko. The Pancreatic Microbiome Is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers. Cancers. 2020; 12 (9):2672.

Chicago/Turabian Style

Jaideep Chakladar; Selena Z. Kuo; Grant Castaneda; Wei Tse Li; Aditi Gnanasekar; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. 2020. "The Pancreatic Microbiome Is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers." Cancers 12, no. 9: 2672.

Journal article
Published: 05 September 2020 in Cancers
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Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes.

ACS Style

Jiayan Ma; Aditi Gnanasekar; Abby Lee; Wei Tse Li; Martin Haas; Jessica Wang-Rodriguez; Eric Y. Chang; Mahadevan Rajasekaran; Weg M. Ongkeko. Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer. Cancers 2020, 12, 2524 .

AMA Style

Jiayan Ma, Aditi Gnanasekar, Abby Lee, Wei Tse Li, Martin Haas, Jessica Wang-Rodriguez, Eric Y. Chang, Mahadevan Rajasekaran, Weg M. Ongkeko. Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer. Cancers. 2020; 12 (9):2524.

Chicago/Turabian Style

Jiayan Ma; Aditi Gnanasekar; Abby Lee; Wei Tse Li; Martin Haas; Jessica Wang-Rodriguez; Eric Y. Chang; Mahadevan Rajasekaran; Weg M. Ongkeko. 2020. "Influence of Intratumor Microbiome on Clinical Outcome and Immune Processes in Prostate Cancer." Cancers 12, no. 9: 2524.

Other
Published: 02 September 2020
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As of 28 August 2020, there have been 5.88 million Coronavirus Disease 2019 (COVID19) cases and 181,000 COVID-19 related deaths in the United States alone. Given the lack of an effective pharmaceutical treatment for COVID-19, the high contagiousness of the disease and its varied clinical outcomes, identifying patients at risk of progressing to severe disease is crucial for the allocation of valuable healthcare resources during this pandemic. Current research has shown that there is a higher prevalence of cardiovascular comorbidities amongst patients with severe COVID-19 or COVID-19-related deaths, but the link between cardiovascular disease and poorer prognosis is poorly understood. We believe that pre-existing immune dysregulation that accompanies cardiovascular disease predisposes patients to a harmful inflammatory immune response, leading to their higher risk of severe disease. Thus, in this project, we aim to characterize immune dysregulation in patients with cardiomyopathy, venous thromboembolism and COVID-19 patients by looking at immune-associated gene dysregulation, immune infiltration and dysregulated immunological pathways and gene signatures.

ACS Style

Grant E Castaneda; Abby C Lee; Wei Tse Li; Chengyu Chen; Jaideep Chakladar; Eric Y. Chang; Weg M. Ongkeko. Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy and venous thromboembolism. 2020, 1 .

AMA Style

Grant E Castaneda, Abby C Lee, Wei Tse Li, Chengyu Chen, Jaideep Chakladar, Eric Y. Chang, Weg M. Ongkeko. Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy and venous thromboembolism. . 2020; ():1.

Chicago/Turabian Style

Grant E Castaneda; Abby C Lee; Wei Tse Li; Chengyu Chen; Jaideep Chakladar; Eric Y. Chang; Weg M. Ongkeko. 2020. "Comparative analysis of immune-associated genes in COVID-19, cardiomyopathy and venous thromboembolism." , no. : 1.

Journal article
Published: 31 July 2020 in International Journal of Molecular Sciences
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The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.

ACS Style

Abby Lee; Jaideep Chakladar; Wei Li; Chengyu Chen; Eric Chang; Jessica Wang-Rodriguez; Weg Ongkeko. Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation. International Journal of Molecular Sciences 2020, 21, 5513 .

AMA Style

Abby Lee, Jaideep Chakladar, Wei Li, Chengyu Chen, Eric Chang, Jessica Wang-Rodriguez, Weg Ongkeko. Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation. International Journal of Molecular Sciences. 2020; 21 (15):5513.

Chicago/Turabian Style

Abby Lee; Jaideep Chakladar; Wei Li; Chengyu Chen; Eric Chang; Jessica Wang-Rodriguez; Weg Ongkeko. 2020. "Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation." International Journal of Molecular Sciences 21, no. 15: 5513.

Preprint content
Published: 13 July 2020
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COVID-19, caused by the virus SARS-CoV-2, has infected millions worldwide. This pandemic overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping, with over 1 billion smokers and vapers worldwide. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined 3 independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cig led to upregulations of pro-inflammatory cytokine production and expression of genes related to inflammasomes. Vaping flavor-less and nicotine-less e-cig, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping, specifically use of flavored or nicotine-containing e-cigs, may critically exacerbate COVID-19-related inflammation or increase susceptibility to the disease. Further scientific and public health investigations should be undertaken to address these concerning links between COVID-19 and e-cig/smoking.

ACS Style

Abby C. Lee; Jaideep Chakladar; Wei Tse Li; Chengyu Chen; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation. 2020, 1 .

AMA Style

Abby C. Lee, Jaideep Chakladar, Wei Tse Li, Chengyu Chen, Eric Y. Chang, Jessica Wang-Rodriguez, Weg M. Ongkeko. Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation. . 2020; ():1.

Chicago/Turabian Style

Abby C. Lee; Jaideep Chakladar; Wei Tse Li; Chengyu Chen; Eric Y. Chang; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2020. "Tobacco, but not nicotine and flavor-less electronic cigarettes, induces ACE2 and immune dysregulation." , no. : 1.

Other
Published: 24 June 2020
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The recent pandemic of Coronavirus Disease 2019 (COVID-19) has placed severe stress on healthcare systems worldwide, which is amplified by the critical shortage of COVID-19 tests. In this study, we propose to generate a more accurate diagnosis model of COVID-19 based on patient symptoms and routine test results by applying machine learning to reanalyzing COVID-19 data from 151 published studies. We aimed to investigate correlations between clinical variables, cluster COVID-19 patients into subtypes, and generate a computational classification model for discriminating between COVID −19 patients and influenza patients based on clinical variables alone. We discovered several novel associations between clinical variables, including correlations between being male and having higher levels of serum lymphocytes and neutrophils. We found that COVID-19 patients could be clustered into subtypes based on serum levels of immune cells, gender, and reported symptoms. Finally, we trained an XGBoost model to achieve a sensitivity of 92.5% and a specificity of 97.9% in discriminating COVID-19 patients from influenza patients. We demonstrated that computational methods trained on large clinical datasets could yield ever more accurate COVID-19 diagnostic models to mitigate the impact of lack of testing. We also presented previously unknown COVID-19 clinical variable correlations and clinical subgroups.

ACS Style

Wei Tse Li; Jiayan Ma; Neil Shende; Grant Castaneda; Jaideep Chakladar; Joseph C. Tsai; Lauren Apostol; Christine O. Honda; Jingyue Xu; Lindsay M. Wong; Tianyi Zhang; Abby Lee; Aditi Gnanasekar; Thomas K. Honda; Selena Z. Kuo; Michael Andrew Yu; Eric Y. Chang; Mahadevan “Raj” Rajasekaran; Weg M. Ongkeko. Using Machine Learning of Clinical Data to Diagnose COVID-19. 2020, 1 .

AMA Style

Wei Tse Li, Jiayan Ma, Neil Shende, Grant Castaneda, Jaideep Chakladar, Joseph C. Tsai, Lauren Apostol, Christine O. Honda, Jingyue Xu, Lindsay M. Wong, Tianyi Zhang, Abby Lee, Aditi Gnanasekar, Thomas K. Honda, Selena Z. Kuo, Michael Andrew Yu, Eric Y. Chang, Mahadevan “Raj” Rajasekaran, Weg M. Ongkeko. Using Machine Learning of Clinical Data to Diagnose COVID-19. . 2020; ():1.

Chicago/Turabian Style

Wei Tse Li; Jiayan Ma; Neil Shende; Grant Castaneda; Jaideep Chakladar; Joseph C. Tsai; Lauren Apostol; Christine O. Honda; Jingyue Xu; Lindsay M. Wong; Tianyi Zhang; Abby Lee; Aditi Gnanasekar; Thomas K. Honda; Selena Z. Kuo; Michael Andrew Yu; Eric Y. Chang; Mahadevan “Raj” Rajasekaran; Weg M. Ongkeko. 2020. "Using Machine Learning of Clinical Data to Diagnose COVID-19." , no. : 1.

Journal article
Published: 21 June 2020 in Cancers
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Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Previous studies have identified the importance of alcohol and hepatitis B (HBV) infection on HCC carcinogenesis, indicating synergy in the methods by which these etiologies advance cancer. However, the specific molecular mechanism behind alcohol and HBV-mediated carcinogenesis remains unknown. Because the microbiome is emerging as a potentially important regulator of cancer development, this study aims to classify the effects of HBV and alcohol on the intratumoral liver microbiome. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance. This abundance was then correlated to clinical variables and to cancer and immune-associated gene expression, in order to determine how microbial abundance may contribute to differing cancer progression between etiologies. We discovered that the liver microbiome is likely oncogenic after exposure to alcohol or HBV, although these etiological factors could decrease the abundance of a few oncogenic microbes, which would lead to a tumor suppressive effect. In HBV-induced tumors, this tumor suppressive effect was inferred based on the downregulation of microbes that induce cancer and stem cell pathways. Alcohol-induced tumors were observed to have distinct microbial profiles from HBV-induced tumors, and different microbes are clinically relevant in each cohort, suggesting that the effects of the liver microbiome may be different in response to different etiological factors. Collectively, our data suggest that HBV and alcohol operate within a normally oncogenic microbiome to promote tumor development, but are also able to downregulate certain oncogenic microbes. Insight into why these microbes are downregulated following exposure to HBV or alcohol, and why the majority of oncogenic microbes are not downregulated, may be critical for understanding whether a pro-tumor liver microbiome could be suppressed or reversed to limit cancer progression.

ACS Style

Jaideep Chakladar; Lindsay M. Wong; Selena Z. Kuo; Wei Tse Li; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B. Cancers 2020, 12, 1642 .

AMA Style

Jaideep Chakladar, Lindsay M. Wong, Selena Z. Kuo, Wei Tse Li, Michael Andrew Yu, Eric Y. Chang, Xiao Qi Wang, Weg M. Ongkeko. The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B. Cancers. 2020; 12 (6):1642.

Chicago/Turabian Style

Jaideep Chakladar; Lindsay M. Wong; Selena Z. Kuo; Wei Tse Li; Michael Andrew Yu; Eric Y. Chang; Xiao Qi Wang; Weg M. Ongkeko. 2020. "The Liver Microbiome Is Implicated in Cancer Prognosis and Modulated by Alcohol and Hepatitis B." Cancers 12, no. 6: 1642.

Journal article
Published: 02 June 2020 in Cancers
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The intra-tumor microbiota has been increasingly implicated in cancer pathogenesis. In this study, we aimed to examine the microbiome in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and determine its compositional differences with relation to age and gender. After grouping 497 LUAD and 433 LUSC patients by age and gender and removing potential contaminants, we identified differentially abundant microbes in each patient cohort vs. adjacent normal samples. We then correlated dysregulated microbes with patient survival rates, immune infiltration, immune and cancer pathways, and genomic alterations. We found that most age and gender cohorts in both LUAD and LUSC contained unique, significantly dysregulated microbes. For example, LUAD-associated Escherichia coli str. K-12 substr. W3110 was dysregulated in older female and male patients and correlated with both patient survival and genomic alterations. For LUSC, the most prominent bacterial species that we identified was Pseudomonas putida str. KT2440, which was uniquely associated with young LUSC male patients and immune infiltration. In conclusion, we found differentially abundant microbes implicated with age and gender that are also associated with genomic alterations and immune dysregulations. Further investigation should be conducted to determine the relationship between gender and age-associated microbes and the pathogenesis of lung cancer.

ACS Style

Lindsay M. Wong; Neil Shende; Wei Tse Li; Grant Castaneda; Lauren Apostol; Eric Y. Chang; Weg M. Ongkeko. Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Cancers 2020, 12, 1447 .

AMA Style

Lindsay M. Wong, Neil Shende, Wei Tse Li, Grant Castaneda, Lauren Apostol, Eric Y. Chang, Weg M. Ongkeko. Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma. Cancers. 2020; 12 (6):1447.

Chicago/Turabian Style

Lindsay M. Wong; Neil Shende; Wei Tse Li; Grant Castaneda; Lauren Apostol; Eric Y. Chang; Weg M. Ongkeko. 2020. "Comparative Analysis of Age- and Gender-Associated Microbiome in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma." Cancers 12, no. 6: 1447.

Journal article
Published: 21 May 2020 in International Journal of Molecular Sciences
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The COVID-19 pandemic is marked by a wide range of clinical disease courses, ranging from asymptomatic to deadly. There have been many studies seeking to explore the correlations between COVID-19 clinical outcomes and various clinical variables, including age, sex, race, underlying medical problems, and social habits. In particular, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature. In this study, we aim to analyze how smoking may affect the SARS-CoV-2 infection rate. We analyzed sequencing data from lung and oral epithelial samples obtained from The Cancer Genome Atlas (TCGA). We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications.

ACS Style

Jaideep Chakladar; Neil Shende; Wei Tse Li; Mahadevan Rajasekaran; Eric Y. Chang; Weg M. Ongkeko. Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility. International Journal of Molecular Sciences 2020, 21, 3627 .

AMA Style

Jaideep Chakladar, Neil Shende, Wei Tse Li, Mahadevan Rajasekaran, Eric Y. Chang, Weg M. Ongkeko. Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility. International Journal of Molecular Sciences. 2020; 21 (10):3627.

Chicago/Turabian Style

Jaideep Chakladar; Neil Shende; Wei Tse Li; Mahadevan Rajasekaran; Eric Y. Chang; Weg M. Ongkeko. 2020. "Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility." International Journal of Molecular Sciences 21, no. 10: 3627.

Journal article
Published: 09 January 2019 in Oncology Letters
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It is clear that alcohol consumption is a major risk factor in the pathogenesis of head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanism underlying the pathogenesis of alcohol-associated HNSCC remains poorly understood. The aim of the present study was to identify and characterize P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) and PIWI proteins dysregulated in alcohol-associated HNSCC to elucidate their function in the development of this cancer. Using next generation RNA-sequencing (RNA-seq) data obtained from 40 HNSCC patients, the piRNA and PIWI protein expression of HNSCC samples was compared between alcohol drinkers and non-drinkers. A separate piRNA expression RNA-seq analysis of 18 non-smoker HNSCC patients was also conducted. To verify piRNA expression, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed on the most differentially expressed alcohol-associated piRNAs in ethanol and acetaldehyde-treated normal oral keratinocytes. The correlation between piRNA expression and patient survival was analyzed using Kaplan-Meier estimators and multivariate Cox proportional hazard models. A comparison between alcohol drinking and non-drinking HNSCC patients demonstrated that a panel of 3,223 piRNA transcripts were consistently detected and differentially expressed. RNA-seq analysis and in vitro RT-qPCR verification revealed that 4 of these piRNAs, piR-35373, piR-266308, piR-58510 and piR-38034, were significantly dysregulated between drinking and non-drinking cohorts. Of these four piRNAs, low expression of piR-58510 and piR-35373 significantly correlated with improved patient survival. Furthermore, human PIWI-like protein 4 was consistently upregulated in ethanol and acetaldehyde-treated normal oral keratinocytes. These results demonstrate that alcohol consumption may cause dysregulation of piRNA expression in HNSCC and in vitro verifications identified 4 piRNAs that may be involved in the pathogenesis of alcohol-associated HNSCC.

ACS Style

Maarouf A. Saad; Jonjei Ku; Selena Z. Kuo; Pin Xue Li; Hao Zheng; Michael Andrew Yu; Jessica Wang‑Rodriguez; Weg M. Ongkeko. Identification and characterization of dysregulated P‑element induced wimpy testis‑interacting RNAs in head and neck squamous cell carcinoma. Oncology Letters 2019, 17, 2615 -2622.

AMA Style

Maarouf A. Saad, Jonjei Ku, Selena Z. Kuo, Pin Xue Li, Hao Zheng, Michael Andrew Yu, Jessica Wang‑Rodriguez, Weg M. Ongkeko. Identification and characterization of dysregulated P‑element induced wimpy testis‑interacting RNAs in head and neck squamous cell carcinoma. Oncology Letters. 2019; 17 (3):2615-2622.

Chicago/Turabian Style

Maarouf A. Saad; Jonjei Ku; Selena Z. Kuo; Pin Xue Li; Hao Zheng; Michael Andrew Yu; Jessica Wang‑Rodriguez; Weg M. Ongkeko. 2019. "Identification and characterization of dysregulated P‑element induced wimpy testis‑interacting RNAs in head and neck squamous cell carcinoma." Oncology Letters 17, no. 3: 2615-2622.

Validation study
Published: 31 May 2017 in PLOS ONE
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Alcohol consumption and chronic hepatitis B virus (HBV) infection are two well-established risk factors for Hepatocellular carcinoma (HCC); however, there remains a limited understanding of the molecular pathway behind the pathogenesis and progression behind HCC, and how alcohol promotes carcinogenesis in the context of HBV+ HCC. Using next-generation sequencing data from 130 HCC patients and 50 normal liver tissues, we identified a panel of microRNAs that are significantly dysregulated by alcohol consumption in HBV+ patients. In particular, two microRNAs, miR-944 and miR-223-3p, showed remarkable correlation with clinical indication and genomic alterations. We confirmed the dysregulation of these two microRNAs in liver cell lines treated by alcohol and acetaldehyde, and showed that manipulation of miR-223-3p and miR-944 expression induces significant changes in cellular proliferation, sensitivity to doxorubicin, and the expression of both direct-binding and downstream mRNA targets. Together, the results of this study suggest that alcohol consumption in HBV+ HCCs regulates microRNAs that likely play previously uncharacterized roles in the alcohol-associated carcinogenesis of HCC, and future studies of these microRNAs may be valuable for furthering the understanding and treatment of alcohol and HBV-associated HCC.

ACS Style

Hao Zheng; Angela E. Zou; Maarouf A. Saad; Xiao Qi Wang; James G. Kwok; Avinaash Korrapati; Pin Xue Li; Tatiana Kisseleva; Jessica Wang-Rodriguez; Weg M. Ongkeko. Alcohol-dysregulated microRNAs in hepatitis B virus-related hepatocellular carcinoma. PLOS ONE 2017, 12, e0178547 .

AMA Style

Hao Zheng, Angela E. Zou, Maarouf A. Saad, Xiao Qi Wang, James G. Kwok, Avinaash Korrapati, Pin Xue Li, Tatiana Kisseleva, Jessica Wang-Rodriguez, Weg M. Ongkeko. Alcohol-dysregulated microRNAs in hepatitis B virus-related hepatocellular carcinoma. PLOS ONE. 2017; 12 (5):e0178547.

Chicago/Turabian Style

Hao Zheng; Angela E. Zou; Maarouf A. Saad; Xiao Qi Wang; James G. Kwok; Avinaash Korrapati; Pin Xue Li; Tatiana Kisseleva; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2017. "Alcohol-dysregulated microRNAs in hepatitis B virus-related hepatocellular carcinoma." PLOS ONE 12, no. 5: e0178547.

Journal article
Published: 08 August 2016 in Oncology Letters
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Alcohol consumption has been implicated in the pathogenesis of head and neck squamous cell carcinoma (HNSCC), although its mechanism is poorly understood. Recent advances in the identification and understanding of long non-coding RNAs (lncRNAs) have indicated that these molecules have a profound effect on numerous biological processes, including tumorigenesis and oncogenesis. The present authors hypothesize that alcohol-mediated dysregulation of lncRNAs is a key event in HNSCC pathogenesis. An in silico differential expression analysis utilizing RNA sequencing (RNA-seq) data from 34 HNSCC patients, which included alcohol drinkers and non-alcohol drinkers, identified a panel of lncRNAs that were dysregulated due to alcohol consumption. Normal oral keratinocytes were then exposed to ethanol and acetaldehyde to validate the RNA-seq results. Two lncRNAs that were differentially expressed due to alcohol consumption were identified from RNA-seq analysis of the clinical data: lnc-PSD4-1 and lnc-NETO-1. Oral keratinocytes exposed to alcohol and acetaldehyde demonstrated dysregulation of these two lncRNAs, thus validating the results of RNA-seq analysis. In addition, low expression of the lnc-PSD4-1 isoform, lnc-PSD4-1:14, exhibited a strong correlation with high survival rates in a Cox proportional hazards regression model. Therefore, these lncRNAs may play a key role in the early pathogenesis of HNSCC, since they are dysregulated in both clinical data and in vitro experiments mimicking the effects of alcohol use.

ACS Style

Vicky Yu; Pranav Singh; Elham Rahimy; Hao Zheng; Selena Z. Kuo; Elizabeth Kim; Jessica Wang-Rodriguez; Weg M. Ongkeko. RNA-seq analysis identifies key long non-coding RNAs connected to the pathogenesis of alcohol-associated head and neck squamous cell carcinoma. Oncology Letters 2016, 12, 2846 -2853.

AMA Style

Vicky Yu, Pranav Singh, Elham Rahimy, Hao Zheng, Selena Z. Kuo, Elizabeth Kim, Jessica Wang-Rodriguez, Weg M. Ongkeko. RNA-seq analysis identifies key long non-coding RNAs connected to the pathogenesis of alcohol-associated head and neck squamous cell carcinoma. Oncology Letters. 2016; 12 (4):2846-2853.

Chicago/Turabian Style

Vicky Yu; Pranav Singh; Elham Rahimy; Hao Zheng; Selena Z. Kuo; Elizabeth Kim; Jessica Wang-Rodriguez; Weg M. Ongkeko. 2016. "RNA-seq analysis identifies key long non-coding RNAs connected to the pathogenesis of alcohol-associated head and neck squamous cell carcinoma." Oncology Letters 12, no. 4: 2846-2853.