Proteins Identified in Metastatic Kidney Cancer

A unique set of proteins have been analyzed that are likely to be involved in the spread of metastatic renal cell carcinoma (RCC).

The discovery will help physicians recognize which tumors are going to behave more aggressively and provide those patients with more intensive treatment and closer follow-up.

Scientists collaborating with pathologists at St. Michael's Hospital (Toronto, ON, Canada) used differential proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling and liquid chromatography and mass spectrometry (LC-MS/MS) analysis to identify proteins that are differentially expressed in metastatic compared to primary RCC. Primary RCC tissues and matched normal kidney tissues from the same patient were obtained from nephrectomy specimens at the hospital and processed.

Western blot analysis, tissue microarray construction and immunohistochemistry were also performed. The team identified 29 proteins that change when cancer cells spread from the original site of the kidney tumor and all 29 proteins have been previously been linked to other malignancies. Of these, 12 were overexpressed (iTRAQ ratios of equal or greater than 1.5) and 17 were under expressed (iTRAQ ratios of equal to or less than 0.67).

The authors concluded that through quantitative proteomic analysis, they had identified differential protein expressions that can distinguish between aggressive and nonaggressive RCC tumors. Many of these proteins are involved in biological pathways pertinent to tumor progression and metastasis. In addition, their preliminary analysis showed that some of these dysregulated proteins may be useful clinical markers and validation of these markers would greatly improve RCC patient treatment and increase overall survival.

George M. Yousef, MD, PhD, the senior author of the study, said “Metastatic renal cell carcinoma is one of the most treatment-resistant malignancies and patients have dismal prognosis. Identification of markers that can predict the potential of metastases will have a great impact on improvement patient outcomes." The study was published on October 17, 2012, in the journal Molecular & Cellular Proteomics.

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