Increased expression of MMP17 predicts poor clinical outcomes in epithelial ovarian cancer patients

Medicine (Baltimore). 2022 Aug 26;101(34):e30279. doi: 10.1097/MD.0000000000030279.

Abstract

Ovarian cancer has the highest fatality rate among female reproductive system cancers, which is due to lack of biomarker for diagnosis and prognosis. We aimed to evaluate the role of matrix metalloproteinase 17 (MMP17) in ovarian cancer tumorigenesis and prognosis. Based on the epithelial ovarian cancer (EOC) in The Cancer Genome Atlas database, we determined the expression of MMP17 using the Wilcoxon rank-sum test. The biological functions of MMP17 were evaluated using the Metascape database and Gene Set Enrichment Analysis. The association between MMP17 and immune cell infiltration was investigated by single sample Gene Set Enrichment Analysis. Logistic analysis was applied to study the correlation between MMP17 expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan-Meier analysis, and nomograms were used to determine the predictive value of MMP17 on clinical outcomes in EOC patients. The expression of MMP17 was much higher in EOC patients than in pericarcinomatous tissues (P < .001). MMP17-associated differentially expressed genes were significantly enriched in cell extracellular matrix (ECM) degrading and corresponding pathways in the high MMP17 expression phenotype. MMP17 has a high sensitivity and specificity for EOC diagnosis, with an area under the curve of 0.988. MMP17 expression was found to be an independent risk factor for overall survival (hazard ratio [HR]: 1.488, P < .001), progression-free interval (HR: 1.347, P < .01), and disease-specific survival (HR: 1.548, P < .01). Increased MMP17 expression in EOC may contribute to carcinogenesis by degrading ECM and provide diagnostic and prognostic value for clinical outcomes.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Ovarian Epithelial* / diagnosis
  • Carcinoma, Ovarian Epithelial* / pathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Matrix Metalloproteinase 17* / metabolism
  • Matrix Metalloproteinases, Membrane-Associated
  • Neoplasms, Glandular and Epithelial*
  • Ovarian Neoplasms* / diagnosis
  • Ovarian Neoplasms* / pathology
  • Prognosis

Substances

  • Biomarkers, Tumor
  • MMP17 protein, human
  • Matrix Metalloproteinase 17
  • Matrix Metalloproteinases, Membrane-Associated