What is the clinical evidence from this study?

Study design: Observational. Population: Multiple cancers. Intervention: Elevated TIMP2 expression. Primary outcome: Survival outcome.

October 18, 2022Open Access

Identification of TIMP2 as a Prognostic Biomarker and Its Correlation with Tumor Immune Microenvironment: A Comprehensive Pan-Cancer Analysis

DWDandan WangNanjing University of Chinese Medicine WXWen‐Xiu XuQingdao University of Science and Technology WCWenquan ChenAnhui Medical University

Key Result

Elevated expression of TIMP2 is associated with unfavorable survival outcomes in multiple cancers.

Study Design

Type

Observational

Structured PICO

Does TIMP2 expression correlate with prognosis and tumor immune microenvironment in cancer patients?

Population

Cancer patients from multiple databases including Oncomine, TCGA, and GTEx

Exposure

Evaluation of TIMP2 expression and mutation status

Outcome

Prognosis and survival outcome in multiple cancerssurrogate

TIMP2 is a potential prognostic biomarker associated with unfavorable survival outcomes and tumor immune microenvironment across various cancers.

Limitations

Concrete mechanisms need to be validated by subsequent experiments.

Abstract

Background: Tissue inhibitor of metalloproteinase-2 (TIMP2), an endogenous inhibitor of matrix metalloproteinases, has been disclosed to participate in the development and carcinogenesis of multiple malignancies. However, the prognosis of TIMP2 in different cancers and its correlation with tumor microenvironment and immunity have not been clarified. Methods: In this study, we conducted a comprehensive bioinformatics analysis to evaluate the prognostic and therapeutic value of TIMP2 in cancer patients by utilizing a series of databases, including Oncomine, GEPIA, cBioPortal, GeneMANIA, Metascape, and Sangerbox online tool. The expression of TIMP2 in different cancers was analyzed by Oncomine, TCGA, and GTEx databases, and mutation status of TIMP2 in cancers was then verified using the cBioPortal database. The protein-protein interaction (PPI) network of the TIMP family was exhibited by GeneMANIA. The prognosis of TIMP2 in cancers was performed though the GEPIA database and Cox regression. Additionally, the correlations between TIMP2 expression and immunity (immune cells, gene markers of immune cells, TMB, MSI, and neoantigen) were explored using Sangerbox online tool. Results: The transcriptional level of TIMP2 in most cancerous tissues was significantly elevated. Survival analysis revealed that an elevated expression of TIMP2 is associated with unfavorable survival outcome in multiple cancers. Enrichment analysis demonstrated the possible mechanisms of TIMPs and their associated genes mainly involved in pathways including extracellular matrix (ECM) regulators, degradation of ECM and ECM disassembly, and several other signaling pathways. Conclusions: Our findings systematically dissected that TIMP2 is a potential prognostic maker in various cancers and use the inhibitor of TIMP2, which may be an effective strategy for cancer therapy to improve the poor cancer survival and prognostic accuracy, but concrete mechanisms need to be validated by subsequent experiments.

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