Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection

Abstract

Background: Although gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance. Materials and Methods: Eligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated. Results: Thirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, four miRNAs were validated using TCGA database. miR-582 was upregulated to a greater extent while miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and miR-100 underexpression were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, miR-100 underexpression, and miR-582 overexpression were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including “invasion and metastasis.” Conclusions: miR-100 underexpression and miR-582 overexpression were associated with gross VI and poor survival of patients after hepatic resection for HCC.