Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2023; 15(10): 1717-1738
Published online Oct 15, 2023. doi: 10.4251/wjgo.v15.i10.1717
Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development
Tai-Liang Lu, Cheng-Long Li, Yong-Qiang Gong, Fu-Tao Hou, Chao-Wu Chen
Tai-Liang Lu, Cheng-Long Li, Yong-Qiang Gong, Fu-Tao Hou, Chao-Wu Chen, Department of General Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China
Author contributions: Lu TL conceived the study, performed the literature search and bioinformatics analysis, and prepared the figures; Li CL, Gong YQ, and Hou FT helped with data collection, analysis, and interpretation; Lu TL and Chen CW wrote and revised the manuscript.
Institutional review board statement: This article is a bioinformatics analysis and does not involve experiments on humans or animals. So Institutional Review Board Approval Form or Document is not applicable.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Data sharing statement: The datasets ANALYZED for this study can be found in The Cancer Genome Atlas (TCGA, https://www.cancer.gov/tcga) and International Cancer Genome Consortium (ICGC, https://www.icgc-argo.org).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chao-Wu Chen, MD, Chief Physician, Department of General Surgery, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61 Jiefang Xi Road, Furong District, Changsha 410005, Hunan Province, China. dr.chencw@hunnu.edu.cn
Received: June 13, 2023
Peer-review started: June 13, 2023
First decision: July 25, 2023
Revised: August 10, 2023
Accepted: September 18, 2023
Article in press: September 18, 2023
Published online: October 15, 2023
Processing time: 118 Days and 16.6 Hours
ARTICLE HIGHLIGHTS
Research background

Primary liver cancer is one of the leading causes of malignant tumor death in China. Hepatocellular carcinoma (HCC) is not sensitive to conventional chemotherapy and radiotherapy. However, drug therapy, represented by targeted therapy and immunotherapy, has progressed dramatically. mRNA vaccines have become an important platform for cancer immunotherapy. mRNA vaccines have been investigated in multiple tumors, but limited studies have been conducted on their use for HCC.

Research motivation

mRNA vaccines are ideally suited for targeting tumor-specific antigens. It is feasible and urgently necessary to develop and apply mRNA vaccines to improve the prognosis of HCC patients. It is also vital to identify HCC patient subpopulations who are suitable for vaccination.

Research objectives

The present study aimed to identify candidate mRNA vaccine antigens for HCC and suitable subpopulations for mRNA vaccination in order to provide new insights into developing HCC mRNA vaccines and screening suitable patients for vaccination.

Research methods

Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas. Genes with somatic mutations and copy number variations were identified by cBioPortal analysis. The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis. The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells (APCs). Tumor-associated antigens were overexpressed in tumors and associated with prognosis, genomic alterations, and APC infiltration. A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes. The weighted gene coexpression network analysis (WGCNA) was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.

Research results

AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 were identified as candidate HCC antigens for mRNA vaccine development. Four immune subtypes (IS1-IS4) and five immune gene modules of HCC were identified that were consistent in both patient cohorts. The immune subtypes showed distinct cellular and clinical characteristics. The IS1 and IS3 immune subtypes were immunologically “cold”. The IS2 and IS4 immune subtypes were immunologically “hot”, and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes. IS1-related modules were identified with the WGCNA algorithm. Ultimately, five hub genes (RBP4, KNG1, METTL7A, F12, and ABAT) were identified, and they might be potential biomarkers for mRNA vaccines.

Research conclusions

AURKA, CCNB1, CDC25C, CDK1, TRIP13, PES1, MCM3, PPM1G, NEK2, KIF2C, PTTG1, KPNA2, and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development. The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination. RBP4, KNG1, METTL7A, F12, and ABAT are potential biomarkers for mRNA vaccines.

Research perspectives

Immunotherapy may be an essential therapeutic tool to improve the clinical outcomes of HCC. The immunotherapy of HCC should be studied in more dimensions.