Wang Dan-Dan, Xu Wen-Xiu, Chen Wen-Quan, Li Lei, Yang Su-Jin, Zhang Jian, Tang Jin-Hai
Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
J Oncol. 2022 Oct 18;2022:9133636. doi: 10.1155/2022/9133636. eCollection 2022.
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.
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.
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.
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.
基质金属蛋白酶组织抑制剂-2（TIMP2）是一种基质金属蛋白酶的内源性抑制剂，已被揭示参与多种恶性肿瘤的发生发展和致癌过程。然而，TIMP2在不同癌症中的预后及其与肿瘤微环境和免疫的相关性尚未明确。
在本研究中，我们通过利用一系列数据库，包括Oncomine、GEPIA、cBioPortal、GeneMANIA、Metascape和Sangerbox在线工具，进行了全面的生物信息学分析，以评估TIMP2在癌症患者中的预后和治疗价值。通过Oncomine、TCGA和GTEx数据库分析TIMP2在不同癌症中的表达，然后使用cBioPortal数据库验证癌症中TIMP2的突变状态。GeneMANIA展示了TIMP家族的蛋白质-蛋白质相互作用（PPI）网络。通过GEPIA数据库和Cox回归分析TIMP2在癌症中的预后。此外，使用Sangerbox在线工具探索TIMP2表达与免疫（免疫细胞、免疫细胞的基因标志物、肿瘤突变负荷、微卫星不稳定性和新抗原）之间的相关性。
大多数癌组织中TIMP2的转录水平显著升高。生存分析显示，TIMP2表达升高与多种癌症的不良生存结局相关。富集分析表明，TIMP及其相关基因的可能机制主要涉及细胞外基质（ECM）调节剂、ECM降解和ECM分解以及其他几个信号通路。
我们的研究结果系统地剖析了TIMP2是各种癌症中的潜在预后标志物，并使用TIMP2抑制剂，这可能是一种改善癌症不良生存和预后准确性的有效癌症治疗策略，但具体机制需要后续实验验证。
