Proteomics identifies possible RCC biomarkers

Proteomic analysis has identified significant differences between the proteins expressed in renal cell carcinoma (RCC) samples and in healthy renal tissue, UK researchers report.

In particular, two proteins identified– Coronin 1A and adipose differentiation-related protein (ADFP) – could potentially be used as diagnostic or prognostic biomarkers for RCC and perhaps as future therapeutic targets, say Ghulam Nabi, from Ninewells Hospital and the University of Dundee, and co-authors.

The development of adjuvant therapies for locally advanced RCC has been hindered by the lack of biomarkers to identify which patients are likely to benefit from non-specific immunotherapy and other treatments, the researchers explain.

For their study, proteins were extracted from tumour samples from eight surgical specimens of T1 to T3 clear cell carcinomas and the surrounding normal kidney tissue. Quantitative label-free proteomics identified 596 proteins with significantly higher (eg, integrin-beta) or lower (eg, metallthionein) expression in the RCC samples than in the healthy tissue.

Immunohistochemistry was then used to focus on the overexpression of Coronin 1A, an actin-remodelling protein known to be overexpressed in breast cancer, and ADFP. Results revealed that Coronin 1A was highly expressed in the infiltrating lymphocytes within the tumour samples examined rather than in the RCC cells themselves.

“This is an interesting observation, as RCC is considered [an] immunogenic malignancy and responds to immunotherapy,” the researchers say, recommending further research is conducted to determine whether Coronin 1A could be used as a blood or urine marker for lymphocytic activation in patients with RCC.

Immunohistochemistry also showed that ADFP was present inside most RCC cells, located in the cytoplasm surrounding lipid droplets that are a known marker for clear cell carcinoma.

Nabi et al write in the British Journal of Cancer that ADFP levels have previously been shown to correlate with clear cell carcinoma differentiation and urinary levels are high in patients with RCC or benign kidney disease.

“Our findings confirm previous reports that ADFP could be a biomarker for diagnosis, predicting prognosis or response to treatment,” they observe.

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