Overexpression of GPC6 and TMEM132D in Early Stage Ovarian Cancer Correlates with CD8+ T-Lymphocyte Infiltration and Increased Patient Survival

Biomed Res Int. 2015:2015:712438. doi: 10.1155/2015/712438. Epub 2015 Sep 13.

Abstract

Infiltration of cytotoxic T-lymphocytes in ovarian cancer is a favorable prognostic factor. Employing a differential expression approach, we have recently identified a number of genes associated with CD8+ T-cell infiltration in early stage ovarian tumors. In the present study, we validated by qPCR the expression of two genes encoding the transmembrane proteins GPC6 and TMEM132D in a cohort of early stage ovarian cancer patients. The expression of both genes correlated positively with the mRNA levels of CD8A, a marker of T-lymphocyte infiltration [Pearson coefficient: 0.427 (p = 0.0067) and 0.861 (p < 0.0001), resp.]. GPC6 and TMEM132D expression was also documented in a variety of ovarian cancer cell lines. Importantly, Kaplan-Meier survival analysis revealed that high mRNA levels of GPC6 and/or TMEM132D correlated significantly with increased overall survival of early stage ovarian cancer patients (p = 0.032). Thus, GPC6 and TMEM132D may serve as predictors of CD8+ T-lymphocyte infiltration and as favorable prognostic markers in early stage ovarian cancer with important consequences for diagnosis, prognosis, and tumor immunobattling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • CD8-Positive T-Lymphocytes / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glypicans / metabolism*
  • Humans
  • Lymphocyte Activation
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology
  • Pennsylvania / epidemiology
  • Prevalence
  • Risk Factors
  • Survival Rate
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • GPC6 protein, human
  • Glypicans
  • Membrane Proteins
  • TMEM132D protein, human