Advancing the diagnosis and classification of renal cell carcinomas

Renal cancer is of concern due to its rising incidence worldwide, with new cases per year expected to climb by as much as 20% by 2030 [1]. Renal neoplasms encompass a variety of malignant and benign tumours with varying prognoses. Accurate classification and diagnosis currently rely on immunohistochemistry to detect known protein markers, in combination with examination of morphological characteristics. Accurate identifications are not always possible, which in turn hinders the delivery of a diagnosis and process to adapted treatment plans. Advanced-stage renal cell carcinomas carry extremely poor prognoses, so improved methods are urgently needed.

High-resolution mass spectrometry (MS) is the cornerstone of proteomics technologies and rapidly evolving tool that promises to drive such methods forward. In MS-based proteomics, large numbers of proteins can be characterised and their absolute amounts measured in solid and liquid biopsies, termed the “total protein approach” (TPA) [2]. Tumours may then be distinguished by the unique concentration ranges of protein biomarkers. With an unparalleled depth of interrogation of tumour proteomes, the technique enables new protein markers of specific neoplasms to be found among the vast number of overexpressed proteins in tumour cells. TPA does not require labelling of the sample or the addition of specific antibodies to the sample, and neither are calibration standards required. While some studies have applied the technique to cell or animal models, only one has been conducted with tissue biopsies from cancer patients [3], whose aim was to elucidate changes in energy metabolism and plasma membrane transport, rather than improve clinical practice and patient outcomes. No previous study has applied TPA to renal neoplasms.