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

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.