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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Chong Li1,2,3,*, Jihan Wang4,*, Junfeng Hao2,*, Baijun Dong5,*, Yi Li6, Xiaoxiao Zhu2, Juan Ding1, Shuangchun Ren1, Heping Zhao4, Song Wu3, Yong Tian2, Guo-Qing Wang1
1The Key Laboratory for Bionics Engineering, Ministry of Education, College of Basic Medical Science, Jilin University, Changchun 130021, China
2Laboratory Animal Center, CAS Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
3The Affiliated Luohu Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen 518000, China
4Clinical Laboratory of Hong-Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China
5Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
6Department of Anesthesiology, Peking University Third Hospital, Beijing 100083, China
*These authors contributed equally to this work
Guo-Qing Wang, email: [email protected]
Yong Tian, email: [email protected]
Song Wu, email: [email protected]
Keywords: renal cell carcinoma, polyglutamylation, CCP6, polyE-DNAJC7, diagnosis biomarker
Received: September 16, 2015 Accepted: February 23, 2016 Published: March 16, 2016
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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