Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei 230022, Anhui, China.
School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei 230032, Anhui, China.
Int Immunopharmacol. 2022 Sep;110:109008. doi: 10.1016/j.intimp.2022.109008. Epub 2022 Jul 2.
Tissue inhibitor of metalloproteinase-2 (TIMP2), a member of tissue inhibitors of the metalloproteinase (TIMP) family is associated with the progression of various 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), TNM plot, Gene Expression Profiling Interactive Analysis (GEPIA) database, and 50 paired gastric cancer tissues. We evaluated the influence of TIMP2 on clinical prognosis using the Kaplan-Meier plotter, the PrognoScan database, GEPIA, and TCGA data. The correlation of TIMP2 with tumor immune infiltrates and the set of gene markers of immune infiltrates was investigated by TIMER and GEPIA. TIMP2 is highly expressed in gastric cancer and slightly 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 types of immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in the 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 infiltration in a variety of cancers, especially colon and gastric cancer patients. Moreover, the expression of TIMP2 potentially contributes to the 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.
组织金属蛋白酶抑制剂 2（TIMP2）是组织金属蛋白酶抑制剂（TIMP）家族的成员，与多种肿瘤的进展有关。然而，TIMP2 与癌症预后和肿瘤浸润淋巴细胞的关系尚不清楚。通过肿瘤免疫估计资源（TIMER）、TNM 图、基因表达谱交互分析（GEPIA）数据库和 50 对胃癌组织分析 TIMP2 的表达。我们使用 Kaplan-Meier 绘图仪、PrognoScan 数据库、GEPIA 和 TCGA 数据评估 TIMP2 对临床预后的影响。通过 TIMER 和 GEPIA 研究了 TIMP2 与肿瘤免疫浸润的相关性以及免疫浸润基因标志物集。TIMP2 在胃癌中高表达，在结肠癌中低表达。高 TIMP2 表达与总生存期（OS，风险比 [HR] = 1.38，95%置信区间 [CI]：[1.16-1.63]；P = 0.0002）和无进展生存期（PFS，HR = 1.39，95%CI：[1.14-1.7]；P = 0.0012）显著相关。具体而言，高 TIMP2 表达与较差的 OS 和 PFS 相关，但与 1 期（OS HR = 1.96，P = 0.29；PFS HR = 0.43，P = 0.19）和 2 期（OS HR = 1.59，P = 0.12；PFS HR = 1.47，P = 0.2）和 N0 期（OS HR = 1.6，P = 0.35；PFS HR = 1.56，P = 0.38）患者的 OS 和 PFS 无关。TIMP2 表达与胃腺癌（STAD）和结肠腺癌（COAD）中不同类型的免疫细胞（包括 CD4+T 细胞、CD8+T 细胞、巨噬细胞、中性粒细胞和树突状细胞）呈显著正相关。此外，TIMP2 表达与不同的免疫标志物集强烈相关。这些结果表明，TIMP2 与多种癌症的预后和免疫浸润水平相关，特别是结肠癌和胃癌患者。此外，TIMP2 的表达可能有助于调节结肠癌和胃癌中的肿瘤相关巨噬细胞（TAMs）、树突状细胞、T 细胞耗竭和 Tregs。这些发现表明，TIMP2 可能作为预测胃癌和结肠癌预后和免疫浸润的预后生物标志物。
