Increased expression of cathepsin L: a novel independent prognostic marker of worse outcome in hepatocellular carcinoma patients

PLoS One. 2014 Nov 10;9(11):e112136. doi: 10.1371/journal.pone.0112136. eCollection 2014.

Abstract

Objectives: To investigate the expression and role of Cathepsin L (CTSL) in Hepatocellular carcinoma (HCC) tissue and cell line (MHCC-97H), and to evaluate the clinical and prognostic significance of CTSL protein in patients with HCC.

Methods: The expression of CTSL was examined in HCC tissue and MHCC-97H cells by Western-blotting, Real-time PCR and immunohistochemical staining. Cell growth curve assay and colony formation assay were used to verify the effect of CTSL on the proliferation and tumor progression ability of MHCC-97H cells. Tumor formation assay in nude mice was used to analyze the effect of CTSL on the tumorigenicity of MHCC-97H cells.

Results: The status of CTSL protein in carcinoma tissues is much higher than that in paracarcinoma tissues. The overall survival of the patients with high CTSL expression was significantly shorter than the low CTSL expression group. high CTSL expression was significantly correlated with advanced clinical staging, histological grade and tumor recurrence. In vitro experiments demonstrated that over-expression of CTSL in MHCC-97H cells promoted cell proliferation and tumor progression ability. Down-regulation of CTSL showed the opposite effects. Over-expression of CTSL increase the tumorigenicity of MHCC-97H cells by in vivo experiments. Moreover, multivariate analysis suggested that CTSL expression might be an independent prognostic indicator for the survival of HCC patients after curative surgery.

Conclusions: CTSL might involve in the development and progression of HCC as a oncogene, and thereby may be a valuable prognostic marker for HCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Cathepsin L / genetics
  • Cathepsin L / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Male
  • Mice
  • Middle Aged
  • Prognosis
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Cathepsin L

Grant support

This project is supported by the National Natural Science Foundation of China (Grant No. 81001212), The Science and Technology Foundation of Zhejiang Province (Grant No. 2012C33011), Foundation of State Key Laboratory of Oncology in South China (Grant No. HN2011-03), Zhejiang Provincial Chinese Medicine Research Foundation (Grant No. 2010ZB062, 2011ZQ012), Foundation of Zhejiang Provincial Educational Committee (Grant No. Y201019175), and Natural Science Foundation of Guangdong (Grant No. s2012010008209). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.