Miao YR, Yang XJ. Hepatocellular carcinoma resistance to tyrosine kinase inhibitors: Current status and perspectives. World J Gastrointest Oncol 2025; 17(4): 101528 [DOI: 10.4251/wjgo.v17.i4.101528]
Corresponding Author of This Article
Xiao-Jun Yang, MD, Associate Professor, Chief Physician, Second Ward of General Surgery, Gansu Province People Hospital, No. 204 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China. yangxjmd@aliyun.com
Research Domain of This Article
Oncology
Article-Type of This Article
Letter to the Editor
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/
World J Gastrointest Oncol. Apr 15, 2025; 17(4): 101528 Published online Apr 15, 2025. doi: 10.4251/wjgo.v17.i4.101528
Hepatocellular carcinoma resistance to tyrosine kinase inhibitors: Current status and perspectives
Yu-Run Miao, Xiao-Jun Yang
Yu-Run Miao, The First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Yu-Run Miao, Xiao-Jun Yang, Second Ward of General Surgery, Gansu Province People Hospital, Lanzhou 730000, Gansu Province, China
Author contributions: Miao YR designed the overall concept and outline of the manuscript; Yang XJ contributed to the discussion and design of the manuscript; Miao YR and Yang XJ contributed to this paper, the writing, and editing the manuscript, and review of literature; all of the authors read and approved the final version of the manuscript to be published.
Supported by The National Health Commission's Key Laboratory of Gastrointestinal Tumor Diagnosis and Treatment for the Year 2022, National Health Commission's Master's and Doctoral/Postdoctoral Fund Project, No. NHCDP2022001; and Gansu Provincial People's Hospital Doctoral Supervisor Training Project, No. 22GSSYA-3.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Xiao-Jun Yang, MD, Associate Professor, Chief Physician, Second Ward of General Surgery, Gansu Province People Hospital, No. 204 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China. yangxjmd@aliyun.com
Received: September 18, 2024 Revised: December 31, 2024 Accepted: January 8, 2025 Published online: April 15, 2025 Processing time: 188 Days and 11.8 Hours
Abstract
The study conducted by Wang et al, focuses on the role of Rho GTPase activating protein 12 (ARHGAP12), in hepatocellular carcinoma (HCC). This research reveals that ARHGAP12 expression, markedly elevated in malignant cells of HCC, correlates strongly with adverse outcomes for patients. Furthermore, the study illustrates that ARHGAP12 enhances the ability of HCC cells to invade and contributes to their resistance to tyrosine kinase inhibitors (TKIs) through modulation of the focal adhesion pathway. To comprehensively investigate the relationship between ARHGAP12 and TKI resistance, this study integrates single-cell and bulk RNA sequencing methodologies along with data from tumor immune single-cell hub 2, Gene Expression Omnibus, The Cancer Genome Atlas, CellMiner, Genomics of Drug Sensitivity in Cancer 2, as well as immunohistochemical staining and proteomic analyses. Statistical analyses, including the Wilcoxon rank-sum test and receiver operating characteristic curve analysis, were employed to evaluate the correlation between ARHGAP12 expression levels and clinical parameters, as well as drug sensitivity. It is evident that a more profound exploration of the molecular dynamics of HCC, especially those related to resistance against TKIs, is essential.
Core Tip: This study reveals the potential clinical value of Rho GTPase activating protein 12 (ARHGAP12) and provided the target direction for clinical tyrosine kinase inhibitor resistance and highlights the potential role of ARHGAP12 in drug resistance by revealing its involvement in the focal adhesion pathway. Through gene enrichment and protein-protein interaction network analyses, it was found that ARHGAP12 might regulate integrin beta 1, impacting cell attachment, migration, and cytoskeleton interactions.
