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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Attenuated RND1 Expression Confers Malignant Phenotype and Predicts Poor Prognosis in Hepatocellular Carcinoma

Hisateru Komatsu1,2, Tomohiro Iguchi1, Takaaki Masuda1

  • 1Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.

Annals of Surgical Oncology
|October 23, 2016
PubMed
Abstract

Insights

Reduced RND1 gene expression in hepatocellular carcinoma (HCC) correlates with poorer prognosis and increased cancer progression. This suggests RND1 may be a novel biomarker for predicting patient outcomes in HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The RND1 gene encodes a Rho GTPase family protein crucial for cellular functions.
  • Decreased RND1 expression is linked to the activation of the oncogenic Ras signaling pathway.
  • Hepatocellular carcinoma (HCC) progression involves complex genetic and signaling alterations.

Purpose of the Study:

  • To determine the clinical significance of RND1 expression in predicting prognosis for HCC patients.
  • To elucidate the biological role of RND1 in the development and progression of human HCC.
  • To investigate the relationship between RND1 and the Ras signaling pathway in HCC.

Main Methods:

  • Analysis of RND1 expression and clinical outcomes in three independent HCC cohorts (n=692).
  • Gene Set Enrichment Analysis (GSEA) to assess pathway correlations.
  • In vitro knockdown experiments using small interfering RNA (siRNA) in HCC cells.

Main Results:

  • RND1 expression decreased with HCC progression and was influenced by promoter methylation.
  • Low RND1 expression was significantly associated with poorer overall survival (OS) and recurrence-free survival.
  • RND1 expression showed an inverse correlation with Ras signaling activity; RND1 knockdown increased HCC cell proliferation, invasion, and chemoresistance.

Conclusions:

  • Reduced RND1 expression in HCC is linked to cancer progression, potentially via Ras signaling pathway regulation.
  • RND1 expression serves as an independent prognostic factor for OS in HCC.
  • RND1 may represent a novel clinical biomarker for predicting HCC patient prognosis.

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