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TIMP1提示肾细胞癌预后不良并加速肿瘤发生的EMT信号通路。

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

作者信息

Shou Yi, Liu Yuenan, Xu Jiaju, Liu Jingchong, Xu Tianbo, Tong Junwei, Liu Lilong, Hou Yaxin, Liu Di, Yang Hongmei, Cheng Gong, Zhang Xiaoping

机构信息

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Genet. 2022 Feb 25;13:648134. doi: 10.3389/fgene.2022.648134. eCollection 2022.

DOI:10.3389/fgene.2022.648134
PMID:35281807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8914045/
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 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.

摘要

肾细胞癌（RCC）是泌尿系统最常见的恶性肿瘤之一。尽管RCC的全身治疗取得了进展，但晚期RCC的死亡率仍然很高。考虑到早期RCC的误诊，鉴定有效的生物标志物非常重要。组织金属蛋白酶抑制剂1（TIMP1）属于TIMP基因家族，是基质金属蛋白酶（MMPs）的天然抑制剂。在本研究中，我们发现TIMP1在细胞系和RCC组织中显著上调。Kaplan-Meier分析显示，TIMP1高表达表明预后不良。多变量分析进一步表明，TIMP1过表达是RCC患者的独立预后因素。此外，敲低TIMP1可抑制RCC细胞的增殖、迁移和侵袭，而上调TIMP1则加速RCC细胞的增殖、迁移和侵袭。此外，我们还发现TIMP1通过上皮-间质转化（EMT）信号通路促进RCC的进展。总之，目前的结果表明，TIMP1提示肾细胞癌预后不良，可作为RCC潜在的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/94ac3eca15c3/fgene-13-648134-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/7aaaa338f2f2/fgene-13-648134-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/c5611ce39eb2/fgene-13-648134-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/2a71069dd24a/fgene-13-648134-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/94ac3eca15c3/fgene-13-648134-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/5286b1018991/fgene-13-648134-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/734b4786d3eb/fgene-13-648134-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/c58fd8a4a39b/fgene-13-648134-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/7aaaa338f2f2/fgene-13-648134-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/c5611ce39eb2/fgene-13-648134-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ffb/8914045/94ac3eca15c3/fgene-13-648134-g009.jpg

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