Quantitative proteomic analysis in metastatic renal cell carcinoma reveals a unique set of proteins with potential prognostic significance.
Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies, and patients have a dismal prognosis, with a <10% five-year survival rate. The identification of markers that can predict the potential for metastases will have a great effect in improving patient outcomes. In this study, we used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to identify proteins that are differentially expressed in metastatic and primary RCC. We identified 1256 non-redundant proteins, and 456 of these were quantified. Further analysis identified 29 proteins that were differentially expressed (12 overexpressed and 17 underexpressed) in metastatic and primary RCC. Dysregulated protein expressions of profilin-1 (Pfn1), 14-3-3 zeta/delta (14-3-3ζ), and galectin-1 (Gal-1) were verified on two independent sets of tissues by means of Western blot and immunohistochemical analysis. Hierarchical clustering analysis showed that the protein expression profile specific for metastatic RCC can distinguish between aggressive and non-aggressive RCC. Pathway analysis showed that dysregulated proteins are involved in cellular processes related to tumor progression and metastasis. Furthermore, preliminary analysis using a small set of tumors showed that increased expression of Pfn1 is associated with poor outcome and is a potential prognostic marker in RCC. In addition, 14-3-3ζ and Gal-1 also showed higher expression in tumors with poor prognosis than in those with good prognosis. Dysregulated proteins in metastatic RCC represent potential prognostic markers for kidney cancer patients, and a greater understanding of their involved biological pathways can serve as the foundation of the development of novel targeted therapies for metastatic RCC.
Department of Chemistry and Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada, M3J 1P3.
Olena
O
Masui
Nicole M A
NM
White
Leroi V
LV
DeSouza
Olga
O
Krakovska
Ajay
A
Matta
Shereen
S
Metias
Bishoy
B
Khalil
Alexander D
AD
Romaschin
R John
RJ
Honey
Robert
R
Stewart
Kenneth
K
Pace
Georg A
GA
Bjarnason
K W Michael
KW
Siu
George M
GM
Yousef
D048948:14-3-3 Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002853:Chromatography, Liquid; D018450:Disease Progression; D037483:Galectin 1 / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis*; D051304:Profilins / Q000378:metabolism; D011379:Prognosis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D053719:Tandem Mass Spectrometry
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D037483:Galectin 1; D009363:Neoplasm Proteins; D051304:Profilins; D020543:Proteome