Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis

PLoS One. 2012;7(12):e52705. doi: 10.1371/journal.pone.0052705. Epub 2012 Dec 20.

Abstract

Background: Autophagy has paradoxical and complex functions in cancer development, and autophagy-related genes (ATG) are key regulators in autophagy. Until now, more than 30 different ATG proteins have been identified in yeast, and their mammalian counterparts also have been reported. Although the roles of a few ATG proteins in cancer have been characterized, the role of ATG10 is almost completely unknown.

Methodology/principal findings: To investigate the clinicopathological role of ATG10 in colorectal cancer, we analyzed ATG10 expression in colorectal cancer tissues and cell lines. Protein expression analysis showed that ATG10 is highly increased in colorectal cancer (tissue - 18/37 cases, 48%; cell line -8/12 cell lines, 66%). Immunohistochemical analysis with clinicopathological features indicated a strong association of the up-regulation of ATG10 with tumor lymph node metastasis (p = 0.005) and invasion (p<0.001). Moreover, both 5-year disease free survival and overall survival rates of patients bearing tumors that did not express ATG10 were significantly higher than those of patients bearing ATG10-expressing tumors (p = 0.012).

Conclusion/significance: Increased expression of ATG10 in colorectal cancer is associated with lymphovascular invasion and lymph node metastasis indicating that ATG10 may be a potential prognostic maker in colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Autophagy-Related Proteins
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Lymphatic Vessels / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Ubiquitin-Conjugating Enzymes / genetics*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Up-Regulation
  • Vesicular Transport Proteins

Substances

  • Autophagy-Related Proteins
  • Vesicular Transport Proteins
  • ATG10 protein, human
  • Ubiquitin-Conjugating Enzymes

Grants and funding

This work was supported by the Center for Development and Commercialization of Anti-Cancer Therapeutics and the Korean Health 21 R&D Project (A062254 and A102059, Ministry of Health, Welfare and Family Affairs, Korea), the Asan Institute for Life Sciences (2011-069), and the Basic Science Research Program (2010-0009164, the National Research Foundation, Korea). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.