scholarly journals iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yushi Zhang ◽  
Yi Cai ◽  
Hongyan Yu ◽  
Hanzhong Li

Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80% of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI 69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC.


Oncotarget ◽  
2014 ◽  
Vol 5 (2) ◽  
pp. 506-518 ◽  
Author(s):  
Nicole M.A. White ◽  
Olena Masui ◽  
Leroi V. DeSouza ◽  
Olga Krakovska ◽  
Shereen Metias ◽  
...  


2012 ◽  
Vol 12 (1) ◽  
pp. 132-144 ◽  
Author(s):  
Olena Masui ◽  
Nicole M. A. White ◽  
Leroi V. DeSouza ◽  
Olga Krakovska ◽  
Ajay Matta ◽  
...  


Tumor Biology ◽  
2014 ◽  
Vol 36 (2) ◽  
pp. 939-951 ◽  
Author(s):  
Zuohui Zhao ◽  
Fei Wu ◽  
Sentai Ding ◽  
Liang Sun ◽  
Zhao Liu ◽  
...  


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 585-585 ◽  
Author(s):  
Patrick Glen Pilie ◽  
Lijun Zhou ◽  
Christine B Peterson ◽  
Yang Peng ◽  
Guang Peng ◽  
...  

585 Background: Clear cell renal cell carcinoma (ccRCC) displays genomic instability across all tumor stages, indicative of increased replicative stress and defects in DNA damage response (DDR) pathways including homologous repair (HR); however ccRCC does not display mutations in canonical DDR genes and advanced ccRCC is not traditionally sensitive to DNA damaging agents. We hypothesized that biallelic VHL loss is sufficient to cause HR deficiency (HRD) and that early stage ccRCC is more likely to display HRD than late stage disease. Methods: We performed whole-exome (WES) sequencing of 15 small ccRCC tumors to assess for mutational burden, mutational signature, and cancer-related driver gene mutations. We performed in silico genomic, transcriptomic, and proteomic analysis of tumors in KIRC TCGA to assess for HRD. Finally, we assessed HR efficiency as a product of biallelic VHL loss in engineered cell line models. Results: 15/15 early stage ccRCC had VHL mutations, approximately 100 additional mutations per tumor, but no common mutations found in KIRC TCGA. In silico analysis showed 67% of KIRC TCGA displayed HRD gene signature, and was significantly higher in stage I disease (p = 2.21e-08). Patients with VHL-mutated tumors are more commonly HRD than HR intact (HRI) (p = 0.03), with frameshift/nonsense variants in VHL more likely to result in HRD than missense variants (p = 0.02). Multivariate analysis showed HRD predicted for better overall survival compared to HRI (p < 0.0001). Proteomic analysis of KIRC TCGA revealed HRI samples had significantly higher protein expression of Rad51 and RAPTOR when compared to HRD samples. Lastly, etoposide-treated MEF Vhl-/- cell lines displayed reduced HR efficiency when compared to Vhl intact controls. Conclusions: Biallelic loss of VHL is sufficient to cause HRD. HRD gene signature predicts for significantly better OS in ccRCC patients, and early stage ccRCC is more likely to be HRD. mTOR/PI3K signaling pathway proteins are differentially expressed in HRI patient samples from TCGA compared to HRD, suggesting a possible role for these oncogenes driving a HRI phenotype. Treatment strategies combining PARP inhibitors with PI3K/mTOR inhibitors should be tested in advanced VHL-mutated ccRCC.





2016 ◽  
Vol 10 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Limin Zhang ◽  
Haowen Jiang ◽  
Gang Xu ◽  
Nan Chu ◽  
Ningxing Xu ◽  
...  


PROTEOMICS ◽  
2008 ◽  
Vol 8 (15) ◽  
pp. 3194-3203 ◽  
Author(s):  
Noboru Okamura ◽  
Taro Masuda ◽  
Akinobu Gotoh ◽  
Toshiro Shirakawa ◽  
Shuji Terao ◽  
...  


2005 ◽  
Vol 173 (4S) ◽  
pp. 98-98
Author(s):  
Richard E. Zigeuner ◽  
Cord Langner ◽  
Peter Rehak ◽  
Marco Auprich ◽  
Katja Lipsky ◽  
...  


2005 ◽  
Vol 20 (3) ◽  
pp. 450 ◽  
Author(s):  
Jeong Seok Hwa ◽  
Hyo Jin Park ◽  
Jae Hun Jung ◽  
Sung Chul Kam ◽  
Hyung Chul Park ◽  
...  


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