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肝细胞癌对酪氨酸激酶抑制剂的耐药性:现状与展望

Hepatocellular carcinoma resistance to tyrosine kinase inhibitors: Current status and perspectives.

作者信息

Miao Yu-Run, Yang Xiao-Jun

机构信息

The First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China.

Second Ward of General Surgery, Gansu Province People Hospital, Lanzhou 730000, Gansu Province, China.

出版信息

World J Gastrointest Oncol. 2025 Apr 15;17(4):101528. doi: 10.4251/wjgo.v17.i4.101528.

Abstract

The study conducted by Wang , 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.

摘要

王所进行的这项研究聚焦于Rho GTP酶激活蛋白12(ARHGAP12)在肝细胞癌(HCC)中的作用。该研究表明,ARHGAP12的表达在HCC恶性细胞中显著升高,与患者的不良预后密切相关。此外,该研究还表明,ARHGAP12增强了HCC细胞的侵袭能力,并通过调节粘着斑途径使其对酪氨酸激酶抑制剂(TKIs)产生抗性。为了全面研究ARHGAP12与TKI抗性之间的关系,本研究整合了单细胞和批量RNA测序方法以及来自肿瘤免疫单细胞中心2、基因表达综合数据库、癌症基因组图谱、CellMiner、癌症药物敏感性基因组学2的数据,以及免疫组织化学染色和蛋白质组学分析。采用包括Wilcoxon秩和检验和受试者工作特征曲线分析在内的统计分析方法来评估ARHGAP12表达水平与临床参数以及药物敏感性之间的相关性。显然,对HCC的分子动力学,尤其是与对TKIs抗性相关的分子动力学进行更深入的探索至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6a0/11995346/8d0361965b74/101528-g001.jpg

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