Cytoskeletal gene alterations linked to sorafenib resistance in hepatocellular carcinoma.

Publisher: BioMed Central Country of Publication: England NLM ID: 101170544 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-7819 (Electronic) Linking ISSN: 14777819 NLM ISO Abbreviation: World J Surg Oncol Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

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

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.
(© 2024. The Author(s).)

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82274034 National Natural Science Foundation of China

Keywords: Cytoskeleton; Drug resistance; Hepatocellular carcinoma; KAS-seq; Sorafenib

9ZOQ3TZI87 (Sorafenib)
0 (Antineoplastic Agents)
0 (Biomarkers, Tumor)

Date Created: 20240607 Date Completed: 20240608 Latest Revision: 20240610

20240610

PMC11157844

10.1186/s12957-024-03417-2

38849867