Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection.
Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection.
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胞浆羧肽酶 6 (CCP6) 水平降低导致血清多谷氨酰化 DNAJC7 蛋白积累：肾细胞癌早期检测的潜在生物标志物
DOI：
10.18632/oncotarget.8107
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发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Wang GQ
中科院分区：
文献类型：
--
作者：
Li C;Wang J;Hao J;Dong B;Li Y;Zhu X;Ding J;Ren S;Zhao H;Wu S;Tian Y;Wang GQ
肾细胞癌（RCC）通常在疾病的晚期被诊断，尽管早期诊断具有更有利的预后。本研究评估了细胞溶质羧肽酶6（CCP 6）的异常表达，导致血清聚谷氨酰化DNAJC 7的积累，作为早期RCC检测的生物标志物。共收集835例RCC、143例慢性肾炎、170例肾结石和415例健康对照，进行CCP 6表达的qRT-PCR、免疫组织化学和Western blot分析以及DNAJC 7和polyglutamylated DNAJC 7的质谱分析。数据显示，在30个RCC组织中CCP 6表达显著降低，质谱和下拉分析鉴定DNAJC 7为CCP 6的底物，并显示RCC患者血清中多聚谷氨酰化DNAJC 7（polyE-DNAJC 7）上调。电化学发光免疫分析法检测805例肾细胞癌患者血清中polyE-DNAJC 7的表达，与385例健康对照组、128例慢性肾炎组和153例肾结石组比较，差异有显著性（p <0.001）。血清DNAJC 7-polyE蛋白水平也与805例晚期RCC患者的分期和分级相关。本研究的数据首次证明血清多聚谷氨酰化DNAJC 7作为RCC早期检测的潜在生物标志物，并与晚期肿瘤分期和分级相关，这为RCC的进一步多聚谷氨酰化研究提供了支持。
Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE-DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC.
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16
作者：
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