Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection.

Abstract

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.

• Authors: Chong Li, Jihan Wang, Junfeng Hao, Baijun Dong, Yi Li, Xiaoxiao Zhu, Juan Ding, Shuangchun Ren, Heping Zhao, Song Wu, Yong Tian, Guo-Qing Wang
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 16 Pg. 22385-96 (Apr 19 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26993597 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• DNAJC7 protein, human
• HSP40 Heat-Shock Proteins
• Heat-Shock Proteins
• Molecular Chaperones
• Carboxypeptidases

Topics

• Adult
• Aged
• Area Under Curve
• Biomarkers, Tumor (blood)
• Carboxypeptidases (metabolism)
• Carcinoma, Renal Cell (blood, diagnosis, pathology)
• Early Detection of Cancer (methods)
• Female
• HSP40 Heat-Shock Proteins (blood)
• Heat-Shock Proteins
• Humans
• Kidney Neoplasms (blood, diagnosis, pathology)
• Male
• Middle Aged
• Molecular Chaperones
• ROC Curve