Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2024; 16(10): 4244-4263
Published online Oct 15, 2024. doi: 10.4251/wjgo.v16.i10.4244
Clinical significance of upregulated Rho GTPase activating protein 12 causing resistance to tyrosine kinase inhibitors in hepatocellular carcinoma
Xiao-Wei Wang, Yu-Xing Tang, Fu-Xi Li, Jia-Le Wang, Gao-Peng Yao, Da-Tong Zeng, Yu-Lu Tang, Bang-Teng Chi, Qin-Yan Su, Lin-Qing Huang, Di-Yuan Qin, Gang Chen, Zhen-Bo Feng, Rong-Quan He
Xiao-Wei Wang, Yu-Xing Tang, Fu-Xi Li, Jia-Le Wang, Gao-Peng Yao, Da-Tong Zeng, Yu-Lu Tang, Qin-Yan Su, Lin-Qing Huang, Gang Chen, Zhen-Bo Feng, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Da-Tong Zeng, Department of Pathology, Red Cross Hospital of Yulin City, Yulin 537000, Guangxi Zhuang Autonomous Region, China
Bang-Teng Chi, Rong-Quan He, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Di-Yuan Qin, Department of Computer Science and Technology, School of Computer and Electronic Information, Guangxi University, Nanning 530004, Guangxi Zhuang Autonomous Region, China
Co-first authors: Xiao-Wei Wang and Yu-Xing Tang.
Co-corresponding authors: Zhen-Bo Feng and Rong-Quan He.
Author contributions: Yao GP, Tang YL, Chen G, Feng ZB, and He RQ conceived and designed the study; Wang XW, Tang YX, Li FX, Wang JL, Zeng DT, Chi BT, Su QY, Huang LQ, and Qin DY performed the experiments, and analyzed the data; Wang XW, Tang YX, Li FX, Wang JL, Yao GP, Zeng DT, Chi BT, and Qin DY wrote the manuscript; Tang YL, Chen G, Feng ZB, and He RQ revised and corrected the draft; and all authors approved the final version of the article. Wang XW and Tang YX are co-first authors, contributing equally in study design, draft writing and data analysis. Wang XW also performed the immunohistochemical experiments and evaluated the corresponding results. Tang YX was responsible for computational pathology, including the calculation of standardized mean difference and summary receiver operating characteristic, as well as the analysis of related pathways. Feng ZB and He RQ are co-corresponding authors, contributing equally in designing the project, supervising various experiments and data mining, and correcting the draft.
Supported by National Natural Science Foundation of China, No. 82260581; Guangxi Zhuang Autonomous Region Health Committee Scientific Research Project, No. Z20201147; Guangxi Medical University Education and Teaching Reform Project, No. 2021XJGA02; Undergraduate Teaching Reform Project of Guangxi Higher Education, No. 2023JGB163; Guangxi Medical University Teacher Teaching Ability Development Project, No. 2202JFA20; and China Undergraduate Innovation and Entrepreneurship Training Program, No. S202310598170.
Institutional review board statement: The study was reviewed and approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University Institutional Review Board, Approval No. 2022-KT-Guoji-127.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset available from the co-first author at tang_yx_patho@163.com. Participants gave informed consent for data sharing.
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: Zhen-Bo Feng, MD, PhD, Professor, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. fengzhenbo_gxmu@163.com
Received: June 24, 2024
Revised: August 17, 2024
Accepted: September 6, 2024
Published online: October 15, 2024
Processing time: 94 Days and 3.1 Hours
Core Tip

Core Tip: Molecular therapy has the potential to reverse tyrosine kinase inhibitors (TKIs) resistance in hepatocellular carcinoma (HCC). We combined 22861 single-cell RNA sequencing malignant cells, 5113 bulk RNA data (bulk RNA-seq and microarrays), and 562 immunohistochemistry samples to explore Rho GTPase activating protein 12 (ARHGAP12) high expression from mRNA and protein. The higher its expression, the worse the prognosis of HCC patients. HCC TKIs showed ARHGAP12 resistance. Mechanistically, we confirmed ARHGAP12 can regulate focal adhesion by combining single-cell RNA sequencing and reconfirmed it from bulk RNA of HCC and HCC TKIs. Drug sensitivity analysis showed that high expression of ARHGAP12 was associated with TKIs resistance, but not with immunotherapy.