Ectopic expression of MECA-79 as a novel prognostic indicator in gastric cancer

Cancer Sci. 2011 May;102(5):1088-94. doi: 10.1111/j.1349-7006.2011.01895.x. Epub 2011 Mar 17.

Abstract

The aim of this study was to clarify the clinical implications of a unique carbohydrate determinant, MECA-79, in gastric cancer specimens and cells. Immunohistochemical analysis showed that 62 of 225 (27.6%) cases were defined as positive for MECA-79. MECA-79 expression was correlated with depth of invasion, venous invasion, TNM stage, and distant metastasis. In survival analyses, patients with MECA-79 expression had worse prognosis by the log-rank test. Multivariate analysis of the Cox proportional hazard model showed that MECA-79 expression was an independent factor of a worse cancer-specific survival. Among 11 gastric cancer cells, MECA-79 was observed in only MKN7 cells, which also expressed GlcNAc6ST-2 transcript. A knockdown of GlcNAc6ST-2 in MKN7 cells showed a markedly reduced expression of MECA-79, suggesting that GlcNAc-sulfation of MECA-79 is mainly synthesized by GlcNAc6ST-2. Furthermore, real-time RT-PCR analysis revealed that GlcNAc6ST-2 was significantly increased in cancer tissues compared with paired normal mucosa. In conclusion, the expression of MECA-79 could be a useful marker for the prognosis of gastric cancer. Our results might also provide novel perspectives on the biology of MECA-79 and GlcNAc6ST-2 in cancer progression and metastasis.

MeSH terms

  • Antigens, Surface / biosynthesis*
  • Biomarkers, Tumor / analysis*
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Membrane Proteins / biosynthesis*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*

Substances

  • Antigens, Surface
  • Biomarkers, Tumor
  • L-selectin counter-receptors
  • Membrane Proteins
  • RNA, Small Interfering