Tissue inhibitor of metalloproteinase-1 (TIMP-1) as a prognostic biomarker in gastrointestinal cancer: a meta-analysis

Lili Qin; Yueqi Wang; Na Yang; Yangyu Zhang; Tianye Zhao; Yanhua Wu; Jing Jiang

doi:10.7717/peerj.10859

Tissue inhibitor of metalloproteinase-1 (TIMP-1) as a prognostic biomarker in gastrointestinal cancer: a meta-analysis

PeerJ. 2021 Feb 16:9:e10859. doi: 10.7717/peerj.10859. eCollection 2021.

Authors

Lili Qin¹, Yueqi Wang¹, Na Yang¹, Yangyu Zhang¹, Tianye Zhao¹, Yanhua Wu¹, Jing Jiang¹

Affiliation

¹ Division of Clinical Research, First Hospital of Jilin University, Changchun, Jilin, China.

Abstract

Background: Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features.

Methods: The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I² test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software.

Results: A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59-2.61], I ² = 35.7%, P _Q = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80-2.28], I ² = 0%, P _Q = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95-4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23-6.04]).

Conclusion: Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.

Keywords: Colorectal cancer; Enzyme linked immunosorbent assay; Gastric cancer; Immunohistochemistry; Meta-analysis; Prognosis; Tissue inhibitor of metalloproteinase 1.

Grants and funding

This work was supported by Science and Technology Department of Jilin Province (20190201093JC, 20200201442JC); the Fundamental Research Funds for the Central Universities; and the Graduate and Innovation Fund of Jilin University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.