TIMP2 is associated with prognosis and immune infiltrates of gastric and colon cancer

Abstract

Tissue inhibitor of metalloproteinase-2 (TIMP2) is an inhibitor among the tissue inhibitors of metalloproteinase (TIMP) family members, is associated with the progression of a variety of tumors. However, the association of TIMP2 with cancer prognosis and tumor-infiltrating lymphocytes remains unclear. TIMP2 expression was analyzed by Tumor Immune Estimation Resource (TIMER), TNMplot, Gene Expression Profiling Interactive Analysis (GEPIA) database and 50 paired gastric cancer tissues. We evaluated the influence of TIMP2 on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database, GEPIA and TCGA data. The correlation of TIMP2 with tumor immune infiltrates and with the set of gene markers of immune infiltrates was investigated by TIMER and GEPIA. TIMP2 is highly expressed in gastric cancer and low expressed in colon cancer. High TIMP2 expression was significantly correlated with poor overall survival (OS, hazard ratio [HR] = 1.38, 95% confidence interval [CI]: [1.16–1.63]; P = 0.0002) and progression-free survival (PFS, HR = 1.39, 95% CI: [1.14–1.7]; P = 0.0012) in gastric cancers. Specifically, high TIMP2 expression was associated with poorer OS and PFS, but not with OS and PFS in stage 1 (OS HR = 1.96, P = 0.29; PFS HR = 0.43, P = 0.19) and stage 2 (OS HR = 1.59, P = 0.12; PFS HR = 1.47, P = 0.2) and stage N0 patients (OS HR = 1.6, P = 0.35; PFS HR = 1.56, P = 0.38) of gastric cancer patients. There was a significant positive correlation between TIMP2 expression and different type of immune cells, including CD4 + T cells, CD8 + T cells, macrophages, Neutrophils, and dendritic cells in stomach adenocarcinoma (STAD) and colon adenocarcinoma (COAD). Moreover, TIMP2 expression was strongly correlated with different sets of immune markers. These results suggest that TIMP2 is associated with prognosis and level of immune infiltrating in a variety of cancers, especially colon and gastric cancer patients. Moreover, expression of TIMP2 potentially contributes to regulation of tumor-associated macrophages (TAMs), dendritic cells, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest that TIMP2 may serve as a prognostic biomarker for predicting prognosis and immune infiltration in gastric and colon cancer.