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.

Highlights

  • Renal cell carcinoma (RCC) is one of the cancer types that originated from the renal epithelium, which accounts for most cancer-related deaths (Hsieh et al, 2017)

  • To determine whether Tissue inhibitor matrix metalloproteinase (TIMP) expression was related to the occurrence and progress of RCC, we downloaded the mRNA of 4 members in this family (TIMP1, TIMP2, TIMP3, and TIMP4) from TCGA_KIRC and drew a heatmap of them according to their mRNA expression

  • All these results indicated that Tissue inhibitor matrix metalloproteinase 1 (TIMP1) might play an important role in RCC progression, which raised our interest to further study

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Summary

Introduction

Renal cell carcinoma (RCC) is one of the cancer types that originated from the renal epithelium, which accounts for most cancer-related deaths (Hsieh et al, 2017). Cancer-specific survival rates at 5 years for the above three types of RCC are 68.9%, 87.4%, and 86.7%, respectively (Cheville et al, 2003; Cinque et al, 2021). The five-year survival rate of early-stage RCC reaches 71%–88%. The survival rate at 5 years of RCC plummets to only 12% when metastasis occurs according to the latest study (Leibovich et al, 2010; Cinque et al, 2021).

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