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基于iTRAQ的定量蛋白质组学分析揭示了透明细胞肾细胞癌潜在的早期诊断标志物。

iTRAQ-based quantitative proteomic analysis reveals potential early diagnostic markers of clear-cell Renal cell carcinoma.

作者信息

Zhang Limin, Jiang Haowen, Xu Gang, Chu Nan, Xu Ningxing, Wen Hui, Gu Bin, Liu Jun, Mao Shanghua, Na Rong, Jing Yan, Ding Qiang, Zhang Yuanfang, Wang Ling

机构信息

Department of Urology, Huashan Hospital, Fudan University.

出版信息

Biosci Trends. 2016 Jul 19;10(3):210-9. doi: 10.5582/bst.2016.01055. Epub 2016 Jun 17.

DOI:10.5582/bst.2016.01055
PMID:27319973
Abstract

Early detection is the key to improve the prognosis of kidney cancer. This study profiled and identified differentially expressed serum proteins in stage T1a renal cell carcinoma (RCC) using isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. A total amount of 99 serum samples including 29 patients with ccRCC, 24 patients with a benign kidney mass, 28 patients with another type of urological tumor (20 cases of transitional cell carcinoma and 8 cases of prostate cancer or a male genital tumor), and 18 healthy controls were subjected to iTRAQ-based mass spectrometry. ProteinPilot software was used to identify the differentially expressed serum proteins in RCC compared to the other three populations. Hierarchical clustering analysis according to The Cancer Genome Atlas (TCGA) RCC database was then performed as the cross-platform validation. Immunohistochemistry was performed to verify the expression of selected proteins in tissue samples from these subjects. iTRAQ identified 27 differentially expressed serum proteins in the RCC patients, and 11 of these proteins were cross validated in RCC tissues from the TCGA database. The expression of C1QC, C1QB, S100A8, S100A9, ceruplasmin, and lumican was verified and associated with the tumor stage and/or grade. There were 27 differentially expressed proteins in early-stage RCC identified by iTRAQ; among them, the expression of C1QC, C1QB, S100A8, S100A9, ceruplasmin, and lumican were associated with the tumor stage and/or grade. Further studies are needed to confirm these data for their use as biomarkers for the early detection of RCC.

摘要

早期检测是改善肾癌预后的关键。本研究使用基于等压标签相对和绝对定量(iTRAQ)的质谱技术,对T1a期肾细胞癌(RCC)患者血清蛋白质进行分析并鉴定差异表达蛋白。共99份血清样本纳入研究,包括29例ccRCC患者、24例肾良性肿块患者、28例其他类型泌尿系统肿瘤患者(20例移行细胞癌和8例前列腺癌或男性生殖系统肿瘤)以及18名健康对照者,均接受基于iTRAQ的质谱分析。使用ProteinPilot软件鉴定RCC患者与其他三组人群相比差异表达的血清蛋白。随后根据癌症基因组图谱(TCGA)RCC数据库进行层次聚类分析作为跨平台验证。采用免疫组织化学法验证这些受试者组织样本中所选蛋白的表达。iTRAQ鉴定出RCC患者中有27种差异表达血清蛋白,其中11种蛋白在TCGA数据库的RCC组织中得到交叉验证。C1QC、C1QB、S100A8、S100A9、铜蓝蛋白和纤连蛋白聚糖的表达得到验证,且与肿瘤分期和/或分级相关。iTRAQ鉴定出早期RCC中有27种差异表达蛋白;其中,C1QC、C1QB、S100A8、S100A9、铜蓝蛋白和纤连蛋白聚糖的表达与肿瘤分期和/或分级相关。需要进一步研究以确认这些数据能否用作RCC早期检测的生物标志物。

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