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TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: A meta-analysis.

ABSTRACT: PURPOSE:Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a glycoprotein involved in cell survival and tumorigenesis. There have been some promising results regarding the diagnostic value of TIMP-1 for patients with colorectal cancer (CRC). The aim of the present study was to assess the diagnostic accuracy and clinical utility of serum TIMP-1 in CRC patients through meta-analysis. METHODS:A systematic search of online databases was performed to collect eligible studies. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operator characteristic (SROC) curve were generated from accuracy data using the random-effects model. Fagan's nomogram and the likelihood matrix were applied to estimate the clinical utility of TIMP-1. RESULTS:A total of 9 eligible studies with 1886 patients were included. Among the patients, 819 were pathologically diagnosed with CRC, whereas 1067 did not have adenomas or other cancers. The overall sensitivity, specificity, and DOR of TIMP-1 for the diagnosis of CRC were 0.65 (95% confidence interval (CI): 0.57-0.72), 0.87 (95% CI: 0.76-0.94), and 12.73 (95% CI 5.71-28.38), respectively. The area under the SROC was 0.77 (95% CI, 0.73-0.81), suggesting the potential diagnostic value of TIMP-1 in CRC patients. Among patients with a pretest CRC probability of 20%, posttest probabilities were 56% and 9% for positive and negative TIMP-1 results, respectively. CONCLUSIONS:TIMP-1 expression exhibits an upper moderate diagnostic value in CRC, and TIMP-1 assessment may be useful as a noninvasive screening tool for CRC in clinical practice.

SUBMITTER: Meng C

PROVIDER: S-EPMC6245680 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: A meta-analysis.

Meng Chunyan C Yin Xiaowei X Liu Jingting J Tang Kaifeng K Tang Hongchao H Liao Jianhua J

PloS one 20181120 11

<h4>Purpose</h4>Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a glycoprotein involved in cell survival and tumorigenesis. There have been some promising results regarding the diagnostic value of TIMP-1 for patients with colorectal cancer (CRC). The aim of the present study was to assess the diagnostic accuracy and clinical utility of serum TIMP-1 in CRC patients through meta-analysis.<h4>Methods</h4>A systematic search of online databases was performed to collect eligible studies. The pool ...[more]

PMID: 30458003

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Project description:Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, -?9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation.We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998-2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test.Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17-2.52, P?=?0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23-2.64, P?=?0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33-0.98, P?=?0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS?=?0.229, P?<?0.001), and TIMP-1 (rS?=?0.280, P?<?0.001) was noted. Among patients showing no systemic inflammatory response, MMP-8 (HR 1.66, 95% CI 1.10-2.53, P?=?0.017) and TIMP-1 (HR 1.59, 95% CI 1.05-2.42, P?=?0.029) were prognostic factors.MMP-8 and TIMP-1 in serum, but not MMP-9, identified CRC patients with bad prognosis. Among patients showing no systemic inflammatory response, MMP-8 and TIMP-1 may associate with poor prognosis.

Project description:BackgroundTissue 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.MethodsThe 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.ResultsA 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]).ConclusionBoth 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.

Dataset Information

TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: A meta-analysis.

Publications

TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: A meta-analysis.

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