Identification and construction of a 13-gene risk model for prognosis prediction in hepatocellular carcinoma patients.

We attempted to screen out the feature genes associated with the prognosis of hepatocellular carcinoma (HCC) patients through bioinformatics methods, to generate a risk model to predict the survival rate of patients. Gene expression information of HCC was accessed from GEO database, and differentially expressed genes (DEGs) were obtained through the joint analysis of multi-chip. Functional and pathway enrichment analyses of DEGs indicated that the enrichment was mainly displayed in biological processes such as nuclear division. Based on TCGA-LIHC data set, univariate, LASSO, and multivariate Cox regression analyses were conducted on the DEGs. Then, 13 feature genes were screened for the risk model. Also, the hub genes were examined in our collected clinical samples and GEPIA database. The performance of the risk model was validated by Kaplan-Meier survival analysis and receiver operation characteristic (ROC) curves. While its universality was verified in GSE76427 and ICGC (LIRI-JP) validation cohorts. Besides, through combining patients' clinical features (age, gender, T staging, and stage) and risk scores, univariate and multivariate Cox regression analyses revealed that the risk score was an effective independent prognostic factor. Finally, a nomogram was implemented for 3-year and 5-year overall survival prediction of patients. Our findings aid precision prediction for prognosis of HCC patients.

Exosome Marker Proteins of Tumor-Associated Fibroblasts and Exosome-Derived miR-92a-3p Act as Potential Biomarkers for Liver Cancer.

Many recent studies have shown that microRNAs (miRNAs) in exosomes can be absorbed by nearby or distant cells, and the abnormal expression of these exosomal miRNAs is associated with most pathological progresses. In this study, we explored the diagnostic value of exosome marker proteins and exosome-derived miR-92a-3p in liver cancer. The clinicopathological data of 60 patients with liver cancer admitted to Tanghan Gongren Hospital from October 2017 to October 2019 were collected. Tumor tissue and adjacent tissue were collected during surgery. Quantitative reverse transcription polymerase chain reaction and Western blot were used to detect the expression levels of miR-92a-3p in exosomes of fibroblasts and tumor tissue, and exosome marker proteins. In liver cancer tissue and fibroblast exosomes, the expression of miR-92a-3p was significantly increased. The receiver operator characteristic curve of the expression level of miR-92a-3p in exosomes and tissue showed that the area under the curve was 0.906 and 0.911, respectively. HSP70 and CD63 were highly expressed in the tissue of liver cancer and fibroblast exosomes. miR-92a-3p was positively correlated with HSP70 and CD63 in the exosomes of liver cancer fibroblasts. In addition, miR-92a-3p and exosome marker proteins (HSP70 and CD63) were highly expressed in tumors with a diameter greater than 5 cm, and were higher in liver cancer patients with BCLC stage B/C. Tumor fibroblast-derived exosome marker proteins and miR-92a-3p have good diagnostic value in liver cancer, indicating that they may be new diagnostic markers for liver cancer.

m5C RNA methyltransferase-related gene NSUN4 stimulates malignant progression of hepatocellular carcinoma and can be a prognostic marker.

Hepatocellular carcinoma (HCC) is a cancer with relatively high mortality, yet little attention has been devoted for related prognostic biomarkers. This study analyzed differential expression of m5C RNA methyltransferase-related genes in normal samples and tumors samples in TCGA-LIHC using Wilcoxon test. K-means consensus clustering analysis was implemented to subdivide samples. Independent prognostic factors were screened by univariate and multivariate Cox regression analyses. KEGG pathway enrichment analysis was performed on the screened independent prognostic factor using GSEA tools. qPCR was conducted to test mRNA expression of key m5C RNA methyltransferase-related genes in tissues and cells. There were 7 m5C RNA methyltransferase-related genes (NOP2, NSUN4, etc.) differentially expressed in HCC tumor tissues. HCC samples were classified into 3 subgroups through clustering analysis according to the expression mode of m5C RNA methyltransferase-related genes. It was also discovered that patients in different subgroups presented significant differences in survival rate and distribution of grade. Additionally, NOP2, NSUN4 and NSUN5 expression notable varied in different grades. Through regression analyses combined with various clinical pathological factors, it was displayed that NSUN4 could work as an independent prognostic factor. KEGG analysis showed that NSUN4 mainly enriched in signaling pathways involved in ADHERENS JUNCTION, RNA DEGRADATION, MTOR SIGNALING PATHWAY, COMPLEMENT and COAGULATION CASCADES. As examined by qPCR, NSUN4 was conspicuously upregulated in HCC patient's tissues and cells. Altogether, our study preliminarily developed a novel biomarker that could be independently used in prognosis of HCC, which may provide a new direction for the study of related molecular mechanism or treatment regimen.

MiR-92a-3p Promotes the Malignant Progression of Hepatocellular Carcinoma by Mediating the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND: As one of the most common cancers globally, hepatocellular carcinoma (HCC) usually has a poor prognosis. Many HCC patients are usually diagnosed at advanced stages. Therefore, new potential biomarkers for the diagnosis and prognosis of HCC are urgently needed. More and more studies have shown that miR-92a-3p can regulate the occurrence and development of various cancers, but its clinical significance and molecular mechanism in HCC are still elusive. Here, we tried to clarify the regulatory mechanism of miR-92a-3p in HCC. METHODS: In this study, we conducted qRT-PCR and revealed that miR-92a-3p was notably upregulated in HCC cells. MTT, flow cytometry, wound healing, Transwell invasion assays and western blot were conducted to uncover that overexpressed miR-92a-3p could boost the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells while inhibiting cell apoptosis. In addition, the proteins associated with the PI3K/AKT/mTOR pathway were also detected by western blot. RESULTS: It was suggested that miR-92a-3p could activate the PI3K/AKT/mTOR signaling pathway. CONCLUSION: These results suggest that miR-92a-3p plays a tumor-promoting role in HCC and may be a potential biomarker for the diagnosis and prognosis of HCC.