Construction and validation of a three-microRNA signature as prognostic biomarker in patients with hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC), a common type of primary liver cancer, is one of the most aggressive malignant tumors worldwide. Although overall survival (OS) rates for HCC has significantly improved in recent years, however, the exact predictive value of microRNA (miRNA) for the prognosis of HCC has not yet been recognized. Here, we aimed to identify potential prognostic miRNAs involved in HCC by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. The RNA expression profiles and corresponding clinical information of HCC were available from The Cancer Genome Atlas (TCGA) datasets. Differentially expression and standardization analysis of miRNAs, Kaplan-Meier curve and time dependent ROC curve were performed by using R tools. Differentially expressed miRNAs (DEmiRNAs) and clinical parameters involved in the OS of HCC were confirmed by Cox regression models. And functional enrichment analysis was used to establish functions of the targeted genes of DEmiRNAs. A total of 300 DEmiRNAs were significantly related with HCC, of which 40 were down-regulated and 260 were up-regulated. A total of 344 patients with DEmiRNAs, status, overall survival (OS) time were randomized into training group (172) and test group (172). Multivariate Cox regression analyses revealed that 3 miRNA (hsa-miR-139-3p, hsa-miR-760, hsa-miR-7-5p) had independent prognostic significance for the OS of HCC in both training and test group. Moreover, according to Kaplan Meier analysis, the OS of HCC patients with high-risk score was shorter in validation and entire series. The time dependent ROC curve demonstrated high accuracy of the signature for OS. Besides, target genes of three miRNAs were analyzed by functional enrichment analysis and 20 genes associated with OS were verified by using Kaplan-Meier method. Compared with normal and benign group, the relative expression level of hsa-miR-139-3p was significantly decreased, while hsa-miR-7-5p and hsa-miR-760 were distinctly increased in the plasma of HCC patients. The same results were observed in the independent cohort. Collectively, our research suggested that three-miRNA signature could serve as an independent prognostic indicator for HCC patients.

Prospective Analysis of Proteins Carried in Extracellular Vesicles with Clinical Outcome in Hepatocellular Carcinoma

“…The purpose of this study was to determine the value of clinical information about proteins carried by extracellular vesicles in HCC based on big data and bioinformatics methods. Bioinformatics research using big data has identified several biomarkers, such as Zhang et al finding that a three-miRNA signature can serve as an independent prognostic indicator for HCC patients [ 35 ], and Du et al revealing that a specific seven-biomarker signature may be clinically useful in predicting HCC prognoses in addition to conventional clinicopathological factors [ 36 ]. While the bioinformatics analysis methods for big data are generally the same, the research perspectives vary.…”

Identification of Conserved Pappalysin 1-Derived Circular RNA-Mediated Competing Endogenous RNA in Osteosarcoma

“…For example, mRNA, miRNA and circRNA were known as the RNA interaction molecules, which have important biological significance. 26 Previous research has reported that the ceRNA was associated with the molecular mechanism of cancers, such as breast cancer, 27 glioblastoma, 28 and lung cancer. 29 Our study performed an integrated analysis of circRNA-associated ceRNAs in >5 OS cell lines.…”

“… 31 Research has found that hsa-miR-760 is upregulated in hepatocellular carcinoma, and it could serve as a potential prognostic miRNAs of hepatocellular carcinoma. 26 However, it has been proved that hsa-miR-760 is downregulated in non-small cell lung cancer, and its expression suppresses the proliferation and metastasis of cells and enhances sensitivity to TNF-related apoptosis-inducing ligand. 32 , 33 These results suggested heterogeneity in tumor pathogenesis.…”

Overview of MicroRNAs as Diagnostic and Prognostic Biomarkers for High-Incidence Cancers in 2021

“…As a result, compared with normal patients, the levels of miRNA-139-3p in the serum of HCC patients decreased, while those of miRNA-7-5p and miRNA-760 increased. Combined with ROC curve analysis, it was indicated that these three miRNAs were also of great diagnostic value for HCC [ 66 ]. Liver transplantation is an effective approach for the treatment of HCC, but there is always a risk of recurrence.…”