High expression of MMP19 is associated with poor prognosis in patients with colorectal cancer

BMC Cancer. 2019 May 14;19(1):448. doi: 10.1186/s12885-019-5673-6.

Abstract

Background: Matrix metalloproteinase 19 (MMP19) is a member of zinc-dependent endopeptidases, which have been involved in various physiological and pathological processes. Its expression has been demonstrated in some types of cancers, but the clinical significance of MMP19 in colorectal cancer (CRC) has not been reported. Thus, we aimed to analyze the clinical significance of MMP19 in CRC in present study.

Methods: The expression of MMP19 was first explored in The Cancer Genome Atlas (TCGA) cohort, and then validated in the GSE39582 cohort and our own database. Clinicopathological features and survival rate were also investigated.

Results: MMP19 was found to be a predictor for overall survival (OS) in both univariate (hazard ratio [HR]: 1.449, 95% confidence interval [CI]: 1.108-1.893, P = 0.007) and multivariate survival analyses (HR: 1.401, 95% CI: 1.036-1.894, P = 0.028) in the TCGA database. MMP19 was further validated as an independent factor for recurrence free survival in the GSE39582 database by both univariate analysis (HR: 2.061, 95%CI: 1.454-2.921, P < 0.001) and multivariate analysis (HR = 1.470, 95% CI: 1.025-2.215, P = 0.032). In an in-house cohort, MMP19 was significantly upregulated in CRC tissues when compared with their adjacent normal controls (P < 0.001). Ectopic MMP19 expression was positively associated with lymph node metastases (P = 0.029), intramural vascular invasion (P = 0.015) and serum carcinoembryonic antigen levels (P = 0.045). High MMP19 expression correlated with a shorter OS (HR = 5.595; 95% CI: 2.573-12.164; P < 0.001) and disease free survival (HR = 4.699; 95% CI: 2.461-8.974; P < 0.001) in multivariate cox regression analysis.

Conclusions: Expression of MMP19 was upregulated in CRC. High expression of MMP19 was determined to be an independent and poor prognostic factor in CRC. These results suggest that MMP19 may be a good biomarker for CRC.

Keywords: Colorectal cancer; MMP19; Survival analysis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinases, Secreted / genetics*
  • Middle Aged
  • Prognosis
  • Up-Regulation*

Substances

  • Biomarkers, Tumor
  • Matrix Metalloproteinases, Secreted
  • matrix metalloproteinase 19