TIMP1 Indicates Poor Prognosis of Renal Cell Carcinoma and Accelerates Tumorigenesis via EMT Signaling Pathway

Abstract

Renal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. The mortality of advanced RCC remains high despite advances in systemic therapy of RCC. Considering the misdiagnosis of early-stage RCC, the identification of effective biomarkers is of great importance. Tissue inhibitor matrix metalloproteinase 1 (TIMP1), which belongs to TIMP gene family, is a natural inhibitor of the matrix metalloproteinases (MMPs). In this study, we found TIMP1 was significantly up-regulated in cell lines and RCC tissues. Kaplan-Meier analysis revealed that high expression of TIMP1 indicated a poor prognosis. Multivariate analysis further indicated that TIMP1 overexpression was an independent prognostic factor of RCC patients. Furthermore, knockdown of TIMP1 in vitro suppressed the proliferation, migration, and invasion of RCC cells, while upregulating TIMP1 accelerated the proliferation, migration, and invasion of RCC cells. In addition, we also found that TIMP1 prompted the progression of RCC via epithelial-to-mesenchymal transition (EMT) signaling pathway. In conclusion, the present results suggested that TIMP1 indicated poor prognosis of renal cell carcinoma and could serve as a potential diagnostic and prognostic biomarker for RCC.