Utility of miR-133a-3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta-analysis and bioinformatics

Abstract

Increasing evidence has demonstrated that microRNA (miR)-133a-3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR-133a-3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR-133a-3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR-133a-3p expression and clinicopathological features of HCC. Eventually, putative targets of miR-133a-3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR-133a-3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=-0.54; 95% confidence interval (CI), -0.74 to -0.35; P<0.001]. Consistently, the level of miR-133a-l in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR-133a-l expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR-133a-3p expression in HCC group was noted (SMD=-0.69; 95% CI, -1.10 to -0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR-133a-3p in HCC. The study reveals that miR-133a-3p may function as a tumor suppressor in HCC. The prospective novel pathways and key genes of miR-133a-3p could offer potential biomarkers for HCC; however, the predictions require further confirmation.