Background: Inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn’s disease, are some of the most common inflammatory disorders of the gastrointestinal tract. The dysfunction of the immune system in the intestines is suggested to be the underlying cause of the pathogenesis of UC. However, the mechanisms regulating these dysfunctional immune cells and inflammatory phenotypes are still unclear.Methods: The differential expression analysis on microarray datasets were performed including GSE24287, GSE87466, GSE102133, and GSE107499, including 376 samples. “Gene Ontology” and “Kyoto Encyclopedia of Genes and Genomes” pathway enrichment analyses were conducted to identify the common differentially expressed genes (DEGs) in these datasets and explore their underlying biological mechanisms. Further algorithms like “Cell-type Identification by Estimating Relative Subsets of RNA Transcripts” were used to determine the infiltration status of immune cells in patients with UC. “Cytoscape” and “Gene Set Enrichment Analysis” were used to screen for hub genes and to investigate their biological mechanisms. The Tumor Immune Estimation Resource database was used to study the correlation between hub genes and infiltrating immune cells in patients with UC. A total of three hub genes, CCL3, MMP3, and TIMP1, were identified using Cytoscape.Results: A positive correlation was observed between these hub genes and patients with active UC. These genes served as a biomarker for active UC. Moreover, a decrease in CCL3, MMP3, and TIMP1 expression was observed in the mucosa of the intestine of patients with active UC who responded to Golimumab therapy. In addition, results show a significant positive correlation between CCL3, MMP3, and TIMP1 expression and different immune cell types including dendritic cells, macrophages, CD8+ T cells, and neutrophils in patients with colon cancer. Moreover, CCL3, MMP3, and TIMP1 expression were strongly correlated with different immune cell markers.Conclusion: Study results show the involvement of hub genes like CCL3, MMP3, and TIMP1 in the pathogenesis of UC. These genes could serve as a novel pharmacological regulator of UC. These could be used as a therapeutic target for treating patients with UC and may serve as biomarkers for immune cell infiltration in colon cancer.

Circulating extracellular vesicles (EVs) are recognized as a promising source of cancer biomarkers. We previously reported that tumor cell-released autophagosomes, a new subgroup of EVs expressing the mature autophagosome-specific marker LC3B (LC3B⁺ EVs), are critical modulators of host anti-tumor immunity. This study aimed to assess the level of plasma LC3B⁺ EVs and the correlation with clinical outcomes in liver cancer patients. The plasma and ascites samples were obtained from patients with liver cancer, non-malignant liver disease, and healthy controls. EVs were isolated by differential centrifugation and characterized using flow cytometry, nanoparticle tracking analysis, transmission electron microscopy, and western blotting. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of plasma LC3B⁺ EVs or HSP90α⁺LC3B⁺ EVs from liver cancer patients. The relationship between the expression levels of HSP90AA1 or MAP1LC3B and survival were analyzed using patient data from the TCGA database. The correlation between HSP90α in LC3B⁺ EVs and PD-1^highCD8⁺ exhausted T cells from the ascites and peripheral blood of liver cancer patients was also evaluated. The EVs preparation from liver cancer patients contained LC3B⁺ EVs expressing epithelial tumor cell adhesion molecules (EpCAM), indicating that these LC3B⁺ EVs originated from epithelial tumor cells. The levels of plasma LC3B⁺ EVs and HSP90α⁺LC3B⁺ EVs in liver cancer patients were significantly higher than in non-malignant liver disease patients and healthy controls. The expression of HSP90α in plasma LC3B⁺ EVs (AUC 0.9595, sensitivity 86.00%, specificity 96.67%) accurately differentiated liver cancer patients from non-liver cancer controls. Additionally, a significant decrease in the levels of plasma LC3B⁺ EVs and HSP90α⁺LC3B⁺ EVs was found post-surgery in each patient, and high expression of HSP90AA1 or MAP1LC3B in the tumor tissue correlated with significantly worse survival compared to those with low expression. We also observed that the level of LC3B⁺ EVs and HSP90α⁺LC3B⁺ EVs positively correlated with the PD-1^highCD8⁺ exhausted T cells in liver cancer patients. Human CD8⁺ T cells treated with purified LC3B⁺ EVs in vitro exhibited a dose-dependent increase in the percentage of PD-1⁺CD8⁺ T cells, whereas the production of IFN-γ was decreased. We demonstrated that isolation and detection of plasma LC3B⁺ EVs carrying bioactive molecules is an effective diagnostic marker of liver cancer, and may also be used as a potential marker for immune monitoring and predicting prognosis clinically.

Background. The CXC chemokines belong to a unique family of chemotactic cytokines that influence the initiation, progression, and clinical outcome of many tumor types. Herein, we investigated the association of the CXC-chemokine ligand 3 (CXCL3) with tumor progression and an unfavorable prognosis for colorectal cancer (CRC). Methods. The quantitative real-time polymerase chain reaction was used to explore the expression of CXCL3 in CRC tissue, adjacent tissue, and plasma. The usefulness of plasma levels of CXCL3 for the diagnosis of CRC was evaluated by receiver operating characteristic curve analysis. Pearson’s correlation analysis assessed relationships among plasma CXCL3, cancer tissue CXCL3, and plasma carcinoembryonic antigen (CEA). Kaplan–Meier analysis was used to assess the survival of CRC patients with high and low expression levels of CXCL3. Survival differences were compared by log-rank test. Results. Initial analysis of the GSE156720 dataset identified CXCL3 as the most enriched CXCL gene in CRC patients. Higher CXCL3 levels were detected in CRC tissue than in adjacent tissue ( ). Compared to healthy controls, CRC patient plasma CXCL3 levels were higher ( ). The area under the curve was 0.81 with a sensitivity of 0.71 and specificity of 0.82, distinguishing CRC from other tumor types. Plasma CXCL3 was positively related to CXCL3 in cancer tissue ( , ), and also to plasma CEA ( , ). Plasma CXCL3 was also related to tumor size ( ), staging ( ), tumor stage ( ), differentiation ( ), and lymph node metastasis ( ), but not to sex ( ), age ( ), tumor site ( ), or distant metastasis ( ). Conclusions. CXCL3 levels were increased in CRC patients, with plasma CXCL3 levels associated with tumor progression and an unfavorable CRC prognosis. The...

Cerebellar degeneration-related protein 1 antisense (CDR1as) is an important member of the circRNAs family, also known as cirs-7. Its main function in vivo is to act as a mir-7 sponge. Accumulated studies show that CDR1as is closely related to various diseases, especially cancer. Our analysis show that CDR1as expression in human cancer is significantly associated with poor overall survival (hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 2.06–3.04; p < 0.00001) and that high CDR1as expression is associated with the tumor node metastasis stage (odds ratio [OR] = 2.13, 95% CI = 1.63–2.78; p < 0.00001), and distant metastasis (OR = 3.50, 95% CI = 1.90–6.64; p < 0.00001). Furthermore, the results reveal the prognostic significance of CDR1as in neoplasms of the digestive system (HR = 1.69, 95% CI = 2.14–2.71; p < 0.001), colorectal cancer (HR = 1.34, 95% CI = 1.96–2.85; p < 0.001), and non-small cell lung cancer (HR = 2.40, 95% CI = 3.42–4.83; p = 0.008). In this study, we summarize in detail the latest research findings and demonstrate the function and regulatory mechanism of CDR1as in various cancer processes, and its potential as a biomarker for cancer prevention and prognosis.

Objective. To evaluate the plasma levels of lnc-DC in primary Sjögren’s syndrome (pSS) patients and investigate the potential associations between lnc-DC and disease activity. Methods. In this study, we recruited 358 enrollments, including 127 pSS patients without immune thrombocytopenia (ITP), 22 pSS patients with ITP, 50 systemic lupus erythematosus (SLE) patients, and 50 patients with rheumatoid arthritis (RA) and 109 healthy individuals, from Xuzhou Central Hospital. The expression of anti-SSA and anti-SSB was detected by enzyme-linked immunosorbent assay (ELISA). Spearman rank correlation test was used to analyze the relationship between lnc-DC and pSS activity. pSS activity was measured by anti-SSA, anti-SSB antibody, erythrocyte sedimentation rate (ESR), and β₂-microglobulin levels. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance of plasma lnc-DC for pSS. Results. Compared with healthy controls, SLE and RA patients, the lnc-DC expression levels were significantly elevated in pSS patients ( ), especially in pSS patients with ITP ( ). As expected, we also found that the lnc-DC expression positively correlated with anti-SSA ( , ), anti-SSB ( , ), ESR level ( , ), and β₂-microglobulin level ( , ) in pSS patients. ROC curves showed that plasma lnc-DC in pSS patients had an AUC 0.80 with a sensitivity of 0.75 and specificity of 0.85 at the optimum cutoff 1.06 in discriminating SLE and RA patients. In addition, the combination of lnc-DC and anti-SSA/SSB (AUC: 0.84, sensitivity: 0.79, specificity: 0.90) improved significantly the diagnostic ability of pSS patients from SLE and RA patients. In the efficacy monitoring study, levels of plasma lnc-DC were dramatically decreased after treatment ( ). Conclusion. These findings highlight that plasma lnc-DC as a novel biomarker for the diagnosis of pSS and can be used to evaluate the therapeutic efficacy of pSS underwent interventional therapy.