MACC1 as a prognostic biomarker for early-stage and AFP-normal hepatocellular carcinoma

PLoS One. 2013 May 23;8(5):e64235. doi: 10.1371/journal.pone.0064235. Print 2013.

Abstract

Background: The metastasis-associated in colon cancer 1 gene (MACC1) has been found to be associated with cancer development and progression. The aim of this study was to investigate the prognostic value of MACC1 in early-stage and AFP-normal hepatocellular carcinoma (HCC).

Methods: mRNA and protein levels of MACC1 expression in one normal liver epithelial cells THLE3 and 15 HCC cell lines were examined using reverse transcription-PCR and Western blot. MACC1 expression was also comparatively studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Immunohistochemistry was employed to analyze MACC1 expression in 308 clinicopathologically characterized HCC cases. Statistical analyses were applied to derive association between MACC1 expression scores and clinical staging as well as patient survival.

Results: Levels of MACC1 mRNA and protein were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. Significant difference in MACC1 expression was found in patients of different TNM stages (P<0.001). Overall survival analysis showed that high MACC1 expression level correlated with lower survival rate (P = 0.001). Importantly, an inverse correlation between MACC1 level and patient survival remained significant in subjects with early-stage HCC or with normal serum AFP level.

Conclusions: MACC1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • Trans-Activators
  • Transcription Factors / metabolism*
  • Up-Regulation
  • alpha-Fetoproteins / metabolism*

Substances

  • MACC1 protein, human
  • Trans-Activators
  • Transcription Factors
  • alpha-Fetoproteins

Grant support

This work was supported by the National Program on Key Basic Research Project (973 Program, No.2012CB519003); The National Science and Technique Major Project (201005022-2, 2012ZX09102101-017, 2012ZX10004213, 311030); The Key Science and Technique Research Project of Guangdong Province (2010B030600003, 2009010058); Natural Science Foundation of China (No. 81071780, 81272198, U1201121, 30900569, 81101864); The Science and Technology Department of Guangdong Province (No. S2011020002757); and Ministry of Education of China (20100171110080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.