A six-miRNA signature as a novel biomarker for improving prediction of prognosis and patterns of immune infiltration in hepatocellular carcinoma

Zhitao Chen; Lele Zhang; Chenchen Ding; Kuiwu Ren; Dalong Wan; Shengzhang Lin

A six-miRNA signature as a novel biomarker for improving prediction of prognosis and patterns of immune infiltration in hepatocellular carcinoma

Am J Transl Res. 2022 Jun 15;14(6):3610-3637. eCollection 2022.

Authors

Zhitao Chen¹, Lele Zhang², Chenchen Ding¹, Kuiwu Ren³, Dalong Wan², Shengzhang Lin^{1

4}

Affiliations

¹ Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College Hangzhou 310004, Zhejiang, China.
² First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou 310003, Zhejiang, China.
³ Fuyang People's Hospital Fuyang 236001, Anhui, China.
⁴ School of Medicine, Zhejiang University City College Hangzhou 310004, Zhejiang, China.

PMID: 35836899
PMCID: PMC9274565

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-related death. MicroRNAs (miRNAs) belong to a subfamily of functional non-coding RNAs (ncRNAs) and are essential regulators of tumorigenesis. They affect tumor-related therapeutic response, tumor metastasis, and clinical outcomes of several human malignant tumors. However, the prognostic value of miRNAs and their role in the tumor immune microenvironment (TIME) of HCC have not been clarified.

Materials and methods: Raw RNA-sequencing data (mRNA and miRNA) and clinicopathological characteristics of HCC samples were downloaded from the TCGA-GDC database. The Perl programming language, R software, Cytoscape software, and several online databases were used to clarify the clinical significance and biological functions of miRNAs and their target genes in HCC.

Results: A total of 424 mRNA-sequencing samples and 425 miRNA-sequencing samples were obtained from the TCGA database. There were 344 HCC cases with complete information in the TCGA dataset and they were randomly categorized into two subgroups. Six miRNAs were identified as independent prognostic biomarkers for HCC patients by univariate and multivariate Cox regression analysis. The constructed prognostic signature, which contains these six miRNAs, was significantly correlated with overall survival (OS). In addition, this prognostic signature is superior to single miRNA in predicting short-term prognosis of HCC patients. We also found that the prognostic signature was significantly associated with tumor-related immune cell infiltration, TIME, and immunotherapeutic response. Furthermore, a total of 4568 potential target genes of six miRNAs were identified. The miRNA-mRNA co-expression network, protein-protein interaction (PPI) network, and functional and pathway enrichment analysis demonstrated that these miRNA-related target genes have important biological effects during the initiation and progression of HCC.

Conclusions: This study demonstrates that the miRNA signature can accurately predict the prognosis of HCC patients and provide a basis for novel immunotherapy treatments.

Keywords: Hepatocellular carcinoma; immunotherapeutic response; miRNA; prognosis; tumor immune microenvironment.