关键词: Cytoskeleton Drug resistance Hepatocellular carcinoma KAS-seq Sorafenib

Mesh : Carcinoma, Hepatocellular / drug therapy genetics pathology Humans Sorafenib / pharmacology therapeutic use Liver Neoplasms / genetics drug therapy pathology Drug Resistance, Neoplasm / genetics Prognosis Antineoplastic Agents / therapeutic use pharmacology Gene Expression Regulation, Neoplastic / drug effects Cytoskeleton / drug effects pathology metabolism Biomarkers, Tumor / genetics Tumor Cells, Cultured Cell Line, Tumor Cell Proliferation / drug effects Gene Expression Profiling

来  源:   DOI:10.1186/s12957-024-03417-2   PDF(Pubmed)

Abstract:
BACKGROUND: Although sorafenib has been consistently used as a first-line treatment for advanced hepatocellular carcinoma (HCC), most patients will develop resistance, and the mechanism of resistance to sorafenib needs further study.
METHODS: Using KAS-seq technology, we obtained the ssDNA profiles within the whole genome range of SMMC-7721 cells treated with sorafenib for differential analysis. We then intersected the differential genes obtained from the analysis of hepatocellular carcinoma patients in GSE109211 who were ineffective and effective with sorafenib treatment, constructed a PPI network, and obtained hub genes. We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients.
RESULTS: In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton.
CONCLUSIONS: The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. Using KAS-seq to analyze the early changes in tumor cells treated with drugs is feasible for studying the drug resistance of tumors, which provides reference significance for future research.
摘要:
背景:尽管索拉非尼一直被用作晚期肝细胞癌(HCC)的一线治疗方法,大多数患者会产生抵抗力,索拉非尼的耐药机制有待进一步研究。
方法:使用KAS-seq技术,我们获得了索拉非尼处理的SMMC-7721细胞全基因组范围内的ssDNA图谱,用于差异分析.然后,我们交叉了从GSE109211肝细胞癌患者分析中获得的差异基因,这些患者使用索拉非尼治疗无效和有效,构建了PPI网络,并获得了hub基因。然后我们剖析了这些基因的表达与肝细胞癌患者预后的关系。
结果:在这项研究中,我们确定了7个中心ERG(ACTB,CFL1、ACTG1、ACTN1、WDR1、TAGLN2、HSPA8)与耐药有关,这些基因与细胞骨架有关。
结论:肝细胞癌中细胞骨架与索拉非尼耐药相关。用KAS-seq分析药物治疗后肿瘤细胞的早期变化,对于研究肿瘤的耐药性是可行的,为今后的研究提供参考意义。
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