Identifying Differentially Expressed MicroRNAs Between Cirrhotic and Non-Cirrhotic Hepatocellular Carcinoma and Exploring Their Functions Using Bioinformatic Analysis

Cellular Physiology and Biochemistry

Ying Mei¹ 

关键词: Cirrhosis;    Hepatocellular carcinoma;    MicroRNA;    Bioinformatic analysis;   

DOI  :  10.1159/000492254

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Few studies have been designed to directly investigate the exact mechanisms underlying the different phenotypes between cirrhotic and non-cirrhotic hepatocellular carcinoma (HCC). This study aimed to illuminate the incidence and developmental mechanisms for both types of HCC through differentially expressed microRNAs (miRNAs) using bioinformatic analysis. Methods The miRNA-seq data and clinical data of patients (from The Cancer Genome Atlas (TCGA) database) were utilized to determine differentially expressed miRNAs between cirrhotic and non-cirrhotic HCC. Afterwards, the function of the selected miRNAs was predicted with online tools. Furthermore, the miRNA expression and clinical significance were validated by external datasets and our experiment. Results The present study included 135 non-cirrhotic and 80 cirrhotic patients to find differentially expressed miRNAs. Among them, four miRNAs (mir-1296, mir-23c, mir-149, and mir-95) were finally selected for further validation and analysis. Correlation analysis found that two miRNAs are greatly associated with the non-cirrhotic HCC patients’ clinical traits, such as the T, M, and N tumor stages. However, only mir-23c was associated with the cirrhotic HCC patients’ tumor T and N stages. Furthermore, survival analysis revealed that increased mir-149 in non-cirrhotic HCC, patients’ age and the existence of vessels in the tumor in cirrhotic HCC were independent risk factors for the patients’ postoperative overall survival. Functional and interaction analyses also supported the notion that these miRNAs function through some pathways that influence the behavior of the HCC. These results are strongly supported by analysis of extra datasets and our experiment. Conclusions The cirrhotic and non-cirrhotic HCC types involve differentially expressed miRNAs, which are correlated with distinctive pathological traits. To some extent, non-cirrhotic HCC seems more dependent on miRNA network regulation, but additional studies are needed to confirm this conclusion.

【 授权许可】

CC BY-NC-ND