Identification of m6A methyltransferase-related lncRNA signature for predicting immunotherapy and prognosis in patients with hepatocellular carcinoma.

Lili Li,Rongrong Xie,Guangrong Lu

doi:10.1042/bsr20210760

Abstract

N6-methyladenosine (m6A) methyltransferase has been shown to be an oncogene in a variety of cancers. Nevertheless, the relationship between the long non-coding RNAs (lncRNAs) and hepatocellular carcinoma (HCC) remains elusive. We integrated the gene expression data of 371 HCC and 50 normal tissues from The Cancer Genome Atlas (TCGA) database. Differentially expressed protein-coding genes (DE-PCGs)/lncRNAs (DE-lncRs) analysis and univariate regression and Kaplan–Meier (K–M) analysis were performed to identify m6A methyltransferase-related lncRNAs. Three prognostic lncRNAs were selected by univariate and LASSO Cox regression analyses to construct the m6A methyltransferase-related lncRNA signature. Multivariate Cox regression analyses illustrated that this signature was an independent prognostic factor for overall survival (OS) prediction. The Gene Set Enrichment Analysis (GSEA) suggested that the m6A methyltransferase-related lncRNAs were involved in the immune-related biological processes (BPs) and pathways. Besides, we discovered that the lncRNAs signature was correlated with the tumor microenvironment (TME) and the expression of critical immune checkpoints. Tumor Immune Dysfunction and Exclusion (TIDE) analysis revealed that the lncRNAs could predict the clinical response to immunotherapy. Our study had originated a prognostic signature for HCC based on the potential prognostic m6A methyltransferase-related lncRNAs. The present study had deepened the understanding of the TME status of HCC patients and laid a theoretical foundation for the choice of immunotherapy.

Highlights

Worldwide, hepatocellular carcinoma (HCC) has become one of the most common malignancies and the second leading cause of cancer-related deaths [1]
Our results showed that this signature was implicated in immune-related terms and pathways that played a key role in HCC tumorigenesis, and was highly connected with the tumor microenvironment (TME) and immunotherapy responses
To identify PCGs and long non-coding RNA (lncRNA) that may be involved in the pathogenesis of HCC, the transcription profiles of HCC patients (n=260) and healthy subjects (n=35) were compared in the training set

Summary

Introduction

Hepatocellular carcinoma (HCC) has become one of the most common malignancies and the second leading cause of cancer-related deaths [1]. HCC is the main pathological type of primary liver cancer, with a global incidence of 500000 new cases and more than 700000 deaths each year [2]. The current curative treatments for early-stage HCC are surgery, thermal ablation, radiofrequency ablation or liver transplantation [4,5,6,7]. For the more than 70% of patients diagnosed with advanced stage, treatments can only provide limited therapeutic benefit for a small subset of patients. Elucidating the molecular mechanisms of HCC and identifying new molecular targets are essential for its diagnosis and treatment

Methods

Results

Conclusion