TIMP1 Indicates Poor Prognosis of Renal Cell Carcinoma and Accelerates Tumorigenesis via EMT Signaling Pathway.
TIMP1 Indicates Poor Prognosis of Renal Cell Carcinoma and Accelerates Tumorigenesis via EMT Signaling Pathway.
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DOI：
10.3389/fgene.2022.648134
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发表时间：
2022
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Shou Y;Liu Y;Xu J;Liu J;Xu T;Tong J;Liu L;Hou Y;Liu D;Yang H;Cheng G;Zhang X
肾细胞癌是泌尿系统最常见的恶性肿瘤之一。尽管肾癌的系统治疗取得了进展，但晚期肾癌的死亡率仍然很高。考虑到早期肾癌易误诊的问题，寻找有效的生物标志物具有重要意义。基质金属蛋白酶组织抑制剂1（TIMP 1）是基质金属蛋白酶（MMPs）的天然抑制剂，属于TIMP基因家族。在本研究中，我们发现TIMP 1在细胞系和RCC组织中显著上调。Kaplan-Meier分析提示TIMP 1高表达提示预后不良。多因素分析进一步表明TIMP 1过表达是影响肾癌患者预后的独立因素。此外，在体外敲低TIMP 1抑制RCC细胞的增殖、迁移和侵袭，而上调TIMP 1促进RCC细胞的增殖、迁移和侵袭。此外，我们还发现TIMP 1通过上皮-间质转化（EMT）信号通路促进RCC的进展。结论：TIMP 1在肾细胞癌中的表达与肾细胞癌的预后密切相关，可作为肾细胞癌诊断和预后的生物学指标。
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.
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DOI：
10.1056/nejmoa1510016
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Choueiri TK;Escudier B;Powles T;Mainwaring PN;Rini BI;Donskov F;Hammers H;Hutson TE;Lee JL;Peltola K;Roth BJ;Bjarnason GA;Géczi L;Keam B;Maroto P;Heng DY;Schmidinger M;Kantoff PW;Borgman-Hagey A;Hessel C;Scheffold C;Schwab GM;Tannir NM;Motzer RJ;METEOR Investigators
通讯作者：
METEOR Investigators
影响因子：
0.7
作者：
Angela Nieto, M.
通讯作者：
Angela Nieto, M.
DOI：
10.15252/embj.2021108647
发表时间：
2021-09-15
期刊：
The EMBO journal
影响因子：
--
作者：
Brabletz S;Schuhwerk H;Brabletz T;Stemmler MP
通讯作者：
Stemmler MP
较高水平的 TIMP-1 表达与三阴性乳腺癌的不良预后相关
影响因子：
37.3
作者：
Cheng G;Fan X;Hao M;Wang J;Zhou X;Sun X
通讯作者：
Sun X
一组长非编码 RNA 在肾细胞癌中表现出诊断和预后价值
影响因子：
5.2
作者：
Cheng, Gong;Liu, Di;Zhang, Xiaoping
通讯作者：
Zhang, Xiaoping