Xu KQ, Gong Z, Yang JL, Xia CQ, Zhao JY, Chen X. B-cell-specific signatures reveal novel immunophenotyping and therapeutic targets for hepatocellular carcinoma. World J Gastroenterol 2024; 30(34): 3894-3925 [DOI: 10.3748/wjg.v30.i34.3894]
Corresponding Author of This Article
Xi Chen, PhD, Research Scientist, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan 430071, Hubei Province, China. chenxi2022@whu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Ke-Quan Xu, Xi Chen, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China
Zheng Gong, Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Jia-Ling Yang, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
Chu-Qi Xia, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
Jian-Yi Zhao, Department of General Surgery, Second People’s Hospital of Jiaozuo City, Jiaozuo 454001, Henan Province, China
Co-first authors: Ke-Quan Xu and Zheng Gong.
Author contributions: Xu KQ, Gong Z and Chen X designed the research; Xu KQ and Gong Z performed the research; Yang JL, Xia CQ and Zhao JY contributed new reagents or analytic tools; Xu KQ, Gong Z and Chen X analyzed the data; Xu KQ, Gong Z and Chen X wrote the paper; All authors contributed to the study design, interpretation of the investigations, data analysis, and manuscript review; Xu KQ and Gong Z are listed as co-first authors because they made equal and significant contributions throughout the research process, being jointly responsible for key aspects such as experimental design and data analysis; Chen X is designated as corresponding author due to his crucial roles in the research design and experimental processes, overseeing the entire study’s planning and supervision, as well as being responsible for interpreting the data and publishing the results; In summary, the authorship order reflects their actual contributions and roles in the research.
Supported bythe Fundamental Research Funds for the Central Universities (2042024YXB009 to X.C.), and Special Foundation for knowledge innovation of Wuhan Science and Technology Innovation Bureau (2023020201020510 to X.C.). Thank you again for your efforts in promoting our article.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The results published here are in whole based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga. All other relevant data can be found in the supplementary material and will be made available on request.
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: Xi Chen, PhD, Research Scientist, Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan 430071, Hubei Province, China. chenxi2022@whu.edu.cn
Received: June 5, 2024 Revised: August 6, 2024 Accepted: August 16, 2024 Published online: September 14, 2024 Processing time: 96 Days and 20.3 Hours
Abstract
BACKGROUND
Immunotherapy presents both promises and challenges in treating hepatocellular carcinoma (HCC) due to its complex immunological microenvironment. The role of B cells, a key part of the immune system, remains uncertain in HCC.
AIM
To identify B-cell-specific signatures and reveal novel immunophenotyping and therapeutic targets for HCC.
METHODS
Using the Tumor Immune Single-cell Hub 2 database, we identified B-cell-related genes (BRGs) in HCC. Gene enrichment analysis was performed to explore the possible collaboration between B cells and T cells in HCC. We conducted univariate Cox regression analysis using The Cancer Genome Atlas liver HCC collection dataset to find BRGs linked to HCC prognosis. Subsequently, least absolute shrinkage and selection operator regression was utilized to develop a prognostic model with 11 BRGs. The model was validated using the International Cancer Genome Consortium dataset and GSE76427.
RESULTS
The risk score derived from the prognostic model emerged as an independent prognostic factor for HCC. Analysis of the immune microenvironment and cell infiltration revealed the immune status of various risk groups, supporting the cooperation of B and T cells in suppressing HCC. The BRGs model identified new molecular subtypes of HCC, each with distinct immune characteristics. Drug sensitivity analysis identified targeted drugs effective for each HCC subtype, enabling precision therapy and guiding clinical decisions.
CONCLUSION
We clarified the role of B cells in HCC and propose that the BRGs model offers promising targets for personalized immunotherapy.
Core tip: We have established a reliable B-cell-related genes (BRGs) prognostic model and novel molecular subtypes in hepatocellular carcinoma (HCC). The BRGs model revealed the immune status and personalized treatment options of HCC molecular subtypes. B cells may play a role in tumor cytotoxicity by activating CD4+ and CD8+ T cells in HCC.
