Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer

Arch Gynecol Obstet. 2018 May;297(5):1235-1244. doi: 10.1007/s00404-018-4699-3. Epub 2018 Feb 10.

Abstract

Objective: Glycoprotein non-metastatic protein B (GPNMB) is a transmembrane glycoprotein that is expressed at higher levels in several malignant human tissues than those in matched normal tissues. Thus, GPNMB may serve as an attractive therapeutic target of cancer treatment. In this study, the prognostic value of GPNMB expression was examined in tumors derived from a cohort of patients with epithelial ovarian cancer (EOC).

Methods: GPNMB expression in matched formalin-fixed and paraffin-embedded tissue samples was evaluated by immunohistochemistry (IHC), whereas GPNMB mRNA expression in fresh-frozen biopsy tissues was detected using real-time quantitative PCR (qPCR). Meanwhile, the correlations of GPNMB expression with the clinical characteristics of EOC were assessed. Besides, survival data were analysed using Kaplan-Meier and Cox regression analyses, respectively.

Results: GPNMB expression was remarkably upregulated in EOC tissues compared with that in normal ovarian controls at both mRNA and protein levels. In addition, abundant GPNMB expression in EOC was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001), residual tumor (P = 0.036), and lymph node metastasis (P = 0.004). Furthermore, results of univariate and multivariate analyses indicated that GPNMB expression level was an independent prognostic factor of the progression-free survival (PFS) and overall survival (OS) (P < 0.001 and P < 0.001, respectively) for EOC patients.

Conclusion: Upregulated GPNMB levels in EOC patients are associated with dismal prognosis. Moreover, findings in the current study indicate that GPNMB is a potentially useful prognostic predictor of the therapeutic approaches for EOC.

Keywords: Epithelial ovarian cancer; GPNMB; Immunohistochemistry; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / metabolism*
  • Carcinoma, Ovarian Epithelial / mortality
  • Carcinoma, Ovarian Epithelial / pathology
  • Cohort Studies
  • Female
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • GPNMB protein, human
  • Membrane Glycoproteins
  • RNA, Messenger