Background: To confirm whether clinical and biochemical parameters or Hashimoto’s thyroiditis (HT) could predict the risks of malignancy among subjects who underwent thyroidectomy, as well as to determine the influence of HT on the biological behavior of papillary thyroid cancer (PTC). Methods: A total of 2,052 patients who underwent initial thyroidectomy were enrolled between June 2006 and August 2008. Serum free T4, free T3, thyrotropin (TSH), thyroglobulin, thyroglobulin antibody, antimicrosomal antibody, tumor-associated status, and thyroid disorders were documented. Results: Binary logistic regression analysis was performed to define the risk predictors for thyroid cancer. Finally, calcification, HT, TSH, and age, were entered into the multivariate model. Multivariate logistic regression analysis revealed the risk of thyroid cancer increases in parallel with TSH concentration within normal range, and the risk for malignancy significantly increased with serum TSH 1.97–4.94 mIU/L, compared with TSH less than 0.35 mIU/L (OR = 1.951, 95% CI = 1.201–3.171, P = 0.007). Increased risks of thyroid cancer were also detected among the patients with HT (OR = 3.732, 95% CI = 2.563–5.435), and microcalcification (OR = 14.486, 95% CI = 11.374–18.449). The effects of HT on the aggressiveness of PTC were not observed in extrathyroidal invasion (P = 0.347), capsular infiltration (P = 0.345), angioinvasion (P = 0.512), and lymph node metastases (P = 0.634). Conclusions: The risk of malignancy increases in patients with higher level TSH within normal range, as well as the presence of HT and microcalcification. No evidence suggests that coexistent HT alleviates the aggressiveness of PTC.

Background: Hepatocellular carcinoma (HCC) is a global health burden with poor prognosis. Anoikis, a novel programmed cell death, has a close interaction with metastasis and progression of cancer. In this study, we aimed to construct a novel bioinformatics model for evaluating the prognosis of HCC based on anoikis-related gene signatures as well as exploring the potential mechanisms.Materials and methods: We downloaded the RNA expression profiles and clinical data of liver hepatocellular carcinoma from TCGA database, ICGC database and GEO database. DEG analysis was performed using TCGA and verified in the GEO database. The anoikis-related risk score was developed via univariate Cox regression, LASSO Cox regression and multivariate Cox regression, which was then used to categorize patients into high- and low-risk groups. Then GO and KEGG enrichment analyses were performed to investigate the function between the two groups. CIBERSORT was used for determining the fractions of 22 immune cell types, while the ssGSEA analyses was used to estimate the differential immune cell infiltrations and related pathways. The “pRRophetic” R package was applied to predict the sensitivity of administering chemotherapeutic and targeted drugs.Results: A total of 49 anoikis-related DEGs in HCC were detected and 3 genes (EZH2, KIF18A and NQO1) were selected out to build a prognostic model. Furthermore, GO and KEGG functional enrichment analyses indicated that the difference in overall survival between risk groups was closely related to cell cycle pathway. Notably, further analyses found the frequency of tumor mutations, immune infiltration level and expression of immune checkpoints were significantly different between the two risk groups, and the results of the immunotherapy cohort showed that patients in the high-risk group have a better immune response. Additionally, the high-risk group was found to have higher sensitivity to 5-fluorouracil, doxorubicin and gemcitabine.Conclusion: The novel signature of 3 anoikis-related genes (EZH2, KIF18A and NQO1) can predict the prognosis of patients with HCC, and provide a revealing insight into personalized treatments in HCC.

In the era of intensity-modulated radiotherapy (IMRT), the role of additional concurrent chemotherapy (CC) to radiotherapy (RT) after induction chemotherapy (IC) compared to IC followed by RT alone remains unclear for stage II-IVB nasopharyngeal carcinoma (NPC) patients. The aim of this study was to evaluate the efficacy and toxicities of IC/RT and IC/CCRT in the treatment of NPC with volumetric modulated arc therapy (VMAT). From January 2012 to March 2016, a total of 217 NPC patients were retrospectively assessed. Of the 217 patients, 139 patients received IC followed by VMAT alone and 78 patients received IC plus CCRT. Overall survival (OS), progression-free survival (PFS) and toxicities were assessed. The 5-year OS, PFS rates were 57.5%, 41.8% and 47.8%, 38.4% for the IC/RT and IC/CCRT arms, respectively, without significant difference in survival between the two groups (both p > 0.05). Multivariate analysis indicated that treatment modality (IC/RT vs. IC/CCRT) was not an independent prognostic factor for OS or PFS. Grade 3–4 leukopenia/neutropenia (3.60% vs. 20.51%, p < 0.001), gastrointestinal disorder (nausea/vomiting/diarrhea, 2.16% vs. 41.03%, p < 0.001), mucositis (29.50% vs. 47.44%, p = 0.01) and xerostomia (34.53% vs. 48.72%, p = 0.04) were more frequent in the IC/ CCRT arm than in the IC/RT arm during VMAT. No significant difference in OS and PFS was observed between IC plus VMAT alone and IC/CCRT in the treatment of stage II-IVB NPC patients, however, more side effects were observed in the IC/CCRT arm.

MicroRNAs play critical roles in tumor progression. Our recent study has indicated that microRNA-7 (miR-7) impairs autophagy-derived pools of glucose to suppress the glycolysis in pancreatic cancer progression. However, the roles of miR-7 in clinical significance and chemoresistance of pancreatic cancer remain unexplored. The aim of this study was to assess the expression of miR-7 in patients with pancreatic cancer and to evaluate the possibility of its usage as a prognostic molecular biomarker. MicroRNA array-based quantification analysis of 372 miRNAs was compared in serum between pancreatic cancer and healthy individuals, gemcitabine-sensitive and gemcitabine-resistance patients. We identified miR-7 showed the potential predictive power for gemcitabine-sensitive patients with pancreatic cancer. Then, the results were validated in pancreatic tissue microarray and The Cancer Genome Atlas (TCGA) dataset, demonstrating that lower miR-7 expression was correlated with more advanced tumor stages and worse prognosis in pancreatic cancer. The Cox proportional-hazards model analysis identified miR-7 to be an independent variable for prediction of the survival. Furthermore, the mechanistic exploration suggested the clinical significance of miR-7 involved its interference effect on autophagy and glycolysis in pancreatic cancer using pancreatic cancer tissue microarrays and TCGA data. Therefore, the results of the present study provide evidences that low microRNA-7 expression may contribute to tumor progression and poor prognosis in pancreatic cancer.

Background: Genomic instability (GI) is among the top ten characteristics of malignancy. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in GI. So far, the clinical value of GI-related lncRNAs (GIlncs) in papillary thyroid cancer (PTC) has not been clarified.Methods: Integrative analysis of lncRNA expression and somatic mutation profiles was performed to identify GIlncs. Analysis of differentially expressed lncRNAs in the group with high- and low- cumulative number of somatic mutations revealed significant GIlncs in PTC. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify hub-GIlncs.Results: A computational model based on four lncRNAs (FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1) was identified as a quantitative index using an in-silicon discovery cohort. GILS score was significantly associated with poor prognosis, as validated in the TCGA dataset and further tested in our local RNA-Seq cohort. Moreover, a combination of clinical characteristics and the composite GILS-clinical prognostic nomogram demonstrates satisfactory discrimination and calibration. Furthermore, the GILS score and FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1 were also associated with driver mutations and multiple clinical-pathological variables, respectively. Moreover, RNA-Seq confirmed the expression patterns of FOXD2-AS1, LINC01614, AC073257.2, and AC005082.1 in PTC and normal thyroid tissues. Biological experiments demonstrated that downregulated or overexpressed LINC01614 affect PTC cell proliferation, migration, and invasion in vitro. Activation of the stromal and immune cell infiltration was also observed in the high LINC01614 group in the PTC microenvironment.Conclusion: In summary, we identified a signature for clinical outcome prediction in PTC comprising four lncRNAs associated with GI. A better understanding of the GI providing an alternative evaluation of the progression risk of PTC. Our study also demonstrated LINC01614 as a novel oncogenic lncRNA and verified its phenotype in PTC.

Senescence is activated in response to gemcitabine to prevent the propagation of cancer cells. However, there is little evidence on whether senescence is involved in gemcitabine resistance in pancreatic cancer. Increasing evidence has demonstrated that microRNAs (miRs) are potential regulators of cellular senescence. The present study aimed to investigate whether aberrant miR‑7 expression modulated senescence to influence pancreatic cancer resistance to chemotherapy. In the present study, cell senescence assay, ALDEFLUOR™ assay, luciferase reporter assay, flow cytometry, quantitative PCR, immunohistochemistry and western blot analysis were performed to explore the association between senescence and gemcitabine therapy response, and to clarify the underlying mechanisms. The present study revealed that gemcitabine‑induced chronically existing senescent pancreatic cells possessed stemness markers. Therapy‑induced senescence led to gemcitabine resistance. Additionally, it was found that miR‑7 expression was decreased in gemcitabine‑resistant pancreatic cancer cells, and that miR‑7 acted as an important regulator of cellular senescence by targeting poly (ADP‑ribose) polymerase 1 (PARP1)/NF‑κB signaling. When miR‑7 expression was restored, it was able to sensitize pancreatic cancer cells to gemcitabine. In conclusion, the present study demonstrated that miR‑7 regulated cellular senescence and relieved gemcitabine resistance by targeting the PARP1/NF‑κB axis in pancreatic cancer cells.