Histo-molecular differentiation of renal cancer subtypes by imaging mass spectrometry and rapid proteome profiling

Summary Background Pathology assessment and differentiation of renal cancer types is challenging due to overlapping histological features of benign and malignant tumors, necessitating high-level expertise. Mass spectrometry (MS) is an emerging tool for tumor classification of clinical tissue sections by spatial histo-molecular imaging or quantitative microproteomics profiling. Results We applied MALDI MS imaging (MSI) and LC-MS/MS-based microproteomics technologies to analyze and classify renal oncocytoma (RO, n=11), clear cell renal cell carcinoma (ccRCC, n=12) and chromophobe renal cell carcinoma (CRCC, n=5). Both methods distinguished ccRCC, RO and CCRC with high accuracy in cross-validation experiments (MSI: 93-95%, LC-MS/MS: 100%). Significance This integrated strategy combining MSI and rapid proteome profiling by LC-MS/MS reveals molecular features of tumor sections and enables cancer subtype classification. Mass spectrometry is a promising complementary approach to current pathological technologies for precise digitized diagnosis of diseases.