Related Experiment Video

Updated: Jun 24, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
00:06

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Cytoskeletal gene alterations linked to sorafenib resistance in hepatocellular carcinoma

Hong Xiao1, Hangyu Chen2, Lei Zhang2

  • 1Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Hainan, China.

World Journal of Surgical Oncology
|June 7, 2024
PubMed
Abstract

Insights

Sorafenib resistance in advanced hepatocellular carcinoma (HCC) is common. This study identifies cytoskeleton-associated genes linked to sorafenib resistance in HCC, offering insights for future therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC).
  • Acquired resistance to sorafenib is a major clinical challenge in HCC treatment.
  • The underlying mechanisms of sorafenib resistance in HCC require further investigation.

Purpose of the Study:

  • To investigate the molecular mechanisms of sorafenib resistance in hepatocellular carcinoma.
  • To identify novel therapeutic targets for overcoming sorafenib resistance.

Main Methods:

  • Utilized KAS-seq technology to analyze single-stranded DNA (ssDNA) profiles in sorafenib-treated SMMC-7721 cells.
  • Integrated differential gene expression data from HCC patients with varying sorafenib responses (GSE109211).
  • Constructed a protein-protein interaction (PPI) network to identify hub genes and analyzed their association with HCC patient prognosis.

Main Results:

  • Identified seven hub differentially expressed genes (ERGs) associated with sorafenib resistance: ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, and HSPA8.
  • These identified hub genes are significantly associated with cytoskeletal functions.
  • The study highlights a correlation between these cytoskeletal genes and patient outcomes in HCC.

Conclusions:

  • The cytoskeleton plays a crucial role in the development of sorafenib resistance in hepatocellular carcinoma.
  • KAS-seq is a viable method for studying early cellular changes in response to drug treatment, aiding in the understanding of tumor drug resistance.
  • This research provides a foundation for developing new strategies to combat sorafenib resistance in HCC.
Keywords:
CytoskeletonDrug resistanceHepatocellular carcinomaKAS-seqSorafenib

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