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

2016 ◽  
Vol 10 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Limin Zhang ◽  
Haowen Jiang ◽  
Gang Xu ◽  
Nan Chu ◽  
Ningxing Xu ◽  
...  
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 8 (4) ◽  
pp. 1040 ◽  
Author(s):  
Francesca Raimondo ◽  
Claudia Salemi ◽  
Clizia Chinello ◽  
Daniela Fumagalli ◽  
Lavinia Morosi ◽  
...  

2019 ◽  
Vol 191 ◽  
pp. 38-47 ◽  
Author(s):  
Martina Stella ◽  
Clizia Chinello ◽  
Anna Cazzaniga ◽  
Andrew Smith ◽  
Manuel Galli ◽  
...  

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 34 (1) ◽  
pp. 5.e11-5.e25 ◽  
Author(s):  
Vanessa Sandim ◽  
Denise de Abreu Pereira ◽  
Dário Eluan Kalume ◽  
Ana Lucia Oliveira-Carvalho ◽  
Antonio Augusto Ornellas ◽  
...  

2020 ◽  
Author(s):  
Jingyuan Wang ◽  
Min Chen ◽  
Chengxue Dang ◽  
Hao Zhang ◽  
Xin Wang ◽  
...  

Abstract Purpose: Clear cell renal cell carcinoma (ccRCC) is a highly lethal cancer that would benefit from non-invasive innovative markers providing early diagnostic and prognostic detection. Increased BIRC5 (baculoviral inhibitor of apoptosis repeat containing 5) expression is associated with negative outcomes or survival in various cancers. Our study aims to investigate the role of BIRC5 of early diagnosis and prognosis in ccRCC by studying the expression of BIRC5 and the correlation between BIRC5 expression and clinicopathological parameters, prognosis in ccRCC. Methods: The BIRC5 expression in ccRCC tissues and normal kidney tissues was measured using the Cancer Genome Atlas (TCGA) database and The Human Protein Atlas database. The correlation between BIRC5 expression and clinicopathological parameters, prognosis in ccRCC was analyzed using UALCAN, Kaplan Meier plotter, GEPIA and SurvExpress. Results: BIRC5 expression is significantly higher in ccRCC than in normal kidney tissues, and is correlated with the clinical stage and pathological grade of ccRCC(P<0.05). The result of analyzing the relationship between BIRC5 expression and outcomes in ccRCC indicates that high BIRC5 expression is an independent prognostic factor affecting overall survival and disease-free survival of ccRCC (P<0.05). Compared with normal kidney tissues, the immunohistochemical test shows that BIRC5 is significantly upregulated in ccRCC tissues. Conclusions: The high expression of BIRC5 is an important indicator of the prognosis of ccRCC, which makes BIRC5 be an effective biomarker for predicting the prognosis of patients in ccRCC. BIRC5 may be a great potential biomarker for early diagnosis of ccRCC.


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

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