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基于定量蛋白质组学和综合生物学评估,PGRMC1是人类肾细胞癌一种新型潜在肿瘤生物标志物。

PGRMC1 Is a Novel Potential Tumor Biomarker of Human Renal Cell Carcinoma Based on Quantitative Proteomic and Integrative Biological Assessments.

作者信息

Zhang Dan, Xia Xiangying, Wang Xixi, Zhang Peng, Lu Weiliang, Yu Yamei, Deng Shi, Yang Hanshuo, Zhu Hongxia, Xu Ningzhi, Liang Shufang

机构信息

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P. R. China.

Department of Urinary Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, P. R. China.

出版信息

PLoS One. 2017 Jan 20;12(1):e0170453. doi: 10.1371/journal.pone.0170453. eCollection 2017.

DOI:10.1371/journal.pone.0170453
PMID:28107520
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5249100/
Abstract

Progesterone receptor membrane component 1 (PGRMC1) is widely observed with an elevated level in multiple human cancers. However, the roles of PGRMC1 in renal cancer are not clear and merit further study. In this report, we made a systematic, integrative biological assessment for PGRMC1 in renal cell carcinoma (RCC) by a quantitative proteomic identification, immunohistochemical detection, and its clinic pathologic significance analysis. We found that PGRMC1 abundance is increased by 3.91-fold in RCC tissues compared with its autologous para-cancerous tissues by a quantitative proteome identification. To validate the proteomic result with more confidence, 135 clinic RCC tissues were recruited to measure PGRMC1 abundance by immunohistochemical staining, and 63.7% RCC samples (n = 86) showed a higher abundance of PGRMC1 than the noncancerous counterparts. And the elevated PGRMC1 level was related to the tumor malignancy degree and overall survival of RCC patients. Meanwhile the average serum PGRMC1 concentration for RCC patients (n = 18) was significantly increased by 1.67 fold compared with healthy persons. Moreover an exogenous elevated abundance of PGRMC1 by plasmid transfections significantly enhanced cell proliferation of renal cancer cells in vitro. Our findings demonstrate PGRMC1, which promotes RCC progression phenotypes in vitro and in vivo, is a novel potential biomarker and therapeutic target for RCC.

摘要

孕激素受体膜成分1(PGRMC1)在多种人类癌症中广泛存在且水平升高。然而,PGRMC1在肾癌中的作用尚不清楚,值得进一步研究。在本报告中,我们通过定量蛋白质组学鉴定、免疫组织化学检测及其临床病理意义分析,对肾细胞癌(RCC)中的PGRMC1进行了系统的综合生物学评估。我们发现,通过定量蛋白质组学鉴定,与癌旁自体组织相比,RCC组织中PGRMC1的丰度增加了3.91倍。为了更有信心地验证蛋白质组学结果,我们收集了135例临床RCC组织,通过免疫组织化学染色测量PGRMC1的丰度,63.7%的RCC样本(n = 86)显示PGRMC1的丰度高于非癌对应组织。PGRMC1水平的升高与RCC患者的肿瘤恶性程度和总生存期相关。同时,RCC患者(n = 18)的血清PGRMC1平均浓度与健康人相比显著增加了1.67倍。此外,通过质粒转染使PGRMC1丰度外源性升高,显著增强了肾癌细胞在体外的增殖。我们的研究结果表明,PGRMC1在体外和体内均促进RCC进展表型,是RCC一种新的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/1048279e3bc5/pone.0170453.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/224a1f0d738c/pone.0170453.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/315b505d441c/pone.0170453.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/affe3ce24e4e/pone.0170453.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/a88fb37763e3/pone.0170453.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/2af3579f9765/pone.0170453.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/1048279e3bc5/pone.0170453.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/224a1f0d738c/pone.0170453.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/315b505d441c/pone.0170453.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/affe3ce24e4e/pone.0170453.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/a88fb37763e3/pone.0170453.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/2af3579f9765/pone.0170453.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4809/5249100/1048279e3bc5/pone.0170453.g006.jpg

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