Identification of potential biomarkers of peripheral blood mononuclear cell in hepatocellular carcinoma using bioinformatic analysis: A protocol for systematic review and meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the cause of an overwhelming number of cancer-related deaths across the world. Developing precise and noninvasive biomarkers is critical for diagnosing HCC. Our research was designed to explore potentially useful biomarkers of host peripheral blood mononuclear cell (PBMC) in HCC by integrating comprehensive bioinformatic analysis. METHODS: Gene expression data of PBMC in both healthy individuals and patients with HCC were extracted from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to annotate the function of DEGs. Protein-protein interaction analysis was performed to screen the hub genes from DEGs. cBioportal database analysis was performed to assess the prognostic significance of hub genes. The Cancer Cell Line Encyclopedia (CCLE) and The Human Protein Atlas (HPA) database analyses were performed to confirm the expression levels of the hub genes in HCC cells and tissue. RESULTS: A total of 95 DEGs were screened. Results of the GO analysis revealed that DEGs were primarily involved in platelet degranulation, cytoplasm, and protein binding. Results of the KEGG analysis indicated that DEGs were primarily enriched in focal adhesion. Five genes, namely, myosin light chain kinase (MYLK), interleukin 1 beta (IL1B), phospholipase D1 (PLD1), cortactin (CTTN), and moesin (MSN), were identified as hub genes. A search in the CCLE and HPA database showed that the expression levels of these hub genes were remarkably increased in the HCC samples. Survival analysis revealed that the overexpression of MYLK, IL1B, and PLD1 may have a significant effect on HCC survival. The aberrant high expression levels of MYLK, IL1B, and PLD1 strongly indicated worse prognosis in patients with HCC. CONCLUSIONS: The identified hub genes may be closely linked with HCC tumorigenicity and may act as potentially useful biomarkers for the prognostic prediction of HCC in PBMC samples.

Association of RASSF1A hypermethylation with risk of HBV/HCV-induced hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Researchers have discovered a large number of DNA methylation patterns in human cancer. These cancer-specific methylation patterns can provide information for the diagnosis, treatment, and prognosis of cancer. Methylation studies can find new biomarkers based on epigenetic analysis and apply these biomarkers to clinical oncology. Many studies on the association between RAASF1A methylation status and susceptibility to hepatitis B virus (HBV)/hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) have reached controversial conclusions. Hence, the current review comprehensively assessed the correlation between Ras association domain family 1A (RASSF1A) methylation and the risk of the HCV/HBV-induced HCC. METHODS: The appropriated publications were extracted in EMBASE, PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure databases using STATA 5.0 software. The odds ratios (ORs) with 95 % confidence interval (95 % CI) of RASSF1A methylation were computed. RESULTS: A total of 1015 HBV/HCV-related HCC samples, 124 non-HBV/HCV-related HCC (NBNC-HCC) samples, and 1225 nontumorous controls were extracted and examined in this research. The frequency of the methylated RASSF1A in the HBV/HCV-related tumor cases displayed a significantly increased OR compared with the overall nontumor samples (OR = 19.372, 95 % CI = 11.060-33.931, P = 0.000). The frequency of the methylated RASSF1A in HBV/HCV-related neoplasm cases displayed a significantly increased OR compared with the non-HBV/HCV-related neoplasm (NBNC-neoplasm) samples (OR = 2.150, 95 % CI = 1.398-3.308, P = 0.000). Compared with normal, chronic hepatitis B or C, cirrhosis, and paracancerous samples, the pooled OR of the RASSF1A promoter methylation in the HBV/HCV-induced HCC samples was 62.785(95 % CI = 35.224-111.909), 25.07 (95 % CI = 13.85-45.36), 6.89 (95 % CI = 3.33-14.264) and 9.02 (95 % CI = 0.91-89.80), respectively. The rate of RASSF1A hypermethylation was robustly correlated with tumor size and vascular invasion, and the pooled OR was 0.346 (95 % CI = 0.210 - 0.569) and 0.081 (95 % CI = 0.022 - 0.303), respectively. CONCLUSION: Results showed robust associations between RASSF1A gene methylation in promoter region and enhanced HBV/HCV-related HCC susceptibility, thereby revealing that RASSF1A methylation status may serve as an important indicator for HCC oncogenesis.

Intake consumption of ginsenoside Rg3, profiling of selected cytokines, and development of rectal polyps.

Background: Rectal polyps is a major risk factor for rectal cancer. There is a need to explore a panel of preventive measures, as well as reliable biomarkers for screening of rectal polyps. Patients and methods: We conducted a case control study which aimed to explore the effects of regular consumption of ginsenoside Rg3, profiling of selected cytokines, and development of rectal polyps in a Chinese population. Results: Significantly higher levels of IL-4, MIP-1ß, FasL, TGF-ß1, and RANTES were detected in rectal polyp cases. Further, we found significant dose-response relationships between quartile-categorized levels of IL-4, MIP-1ß, FasL, and TGF-ß1, and risk of rectal polyps. The strongest associations for IL-4, MIP-1ß, FasL, and TGF-ß1 were observed for the highest quartile vs the lowest quartile with an OR of 1.78, 2.70, 1.49, and 2.36, respectively. Compared with non-Rg3 consumers, regular Rg3 consumers had a significantly lower risk of rectal polyps (OR =0.71; 95% CI: 0.55-0.92; P=0.009). We also found that Rg3 consumers had significantly lower levels of IL-4, MIP-1ß, FasL, and TGF-ß1 than non-Rg3 consumers, in both rectal polyp cases and healthy controls. Conclusion: These results indicate that regular consumption of Rg3 might prevent the occurrence of rectal polyps through decreasing the serum level of selected cytokines, including IL-4, MIP-1ß, FasL, and TGF-ß1. Further clinical trials and prospective cohort studies with larger sample sizes are warranted to validate the anti-inflammatory activity and the anti-tumorigenic role of Rg3.