Integrated analysis of proteome and transcriptome profiling reveals pan-cancer-associated pathways and molecular biomarkers.

Abstract

Understanding dysregulated genes and pathways in cancer is critical for precision oncology. Integrating mass spectrometry-based proteomic data with transcriptomic data presents unique opportunities for systematic analyses of dysregulated genes and pathways in pan-cancer. Here, we compiled a comprehensive set of datasets, encompassing proteomic data from 2,404 samples and transcriptomic data from 7,752 samples across 13 cancer types. Comparisons between normal or adjacent normal tissues (ANTs) and tumor tissues identified several dysregulated pathways including mRNA splicing, interferon pathway, fatty acid metabolism, and complement coagulation cascade in pan-cancer. Additionally, pan-cancer up- and down-regulated genes (PCUGs and PCDGs) were also identified. Notably, RRM2 and ADH1B, two genes belong to PCUGs and PCDGs, respectively, were identified as robust pan-cancer diagnostic biomarkers. TNM stage-based comparisons revealed dysregulated genes and biological pathways involved in cancer progression, among which the dysregulation of complement coagulation cascade and epithelial-mesenchymal transition are frequent in multiple types of cancers. A group of pan-cancer continuously up- and down-regulated proteins in different tumor stages (PCCUPs and PCCDPs) were identified. We further constructed prognostic risk stratification models for corresponding cancer types based on dysregulated genes, which effectively predict the prognosis for patients with these cancers. Drug prediction based on PCUPs and PCDPs as well as PCCUPs and PCCDPs revealed that small molecule inhibitors targeting CDK, HDAC, MEK, JAK, PI3K, and others might be effective treatments for pan-cancer, thereby supporting drug repurposing. We also developed web tools for cancer diagnosis, pathologic stage assessment, and risk evaluation. Overall, this study highlights the power of combining proteomic and transcriptomic data to identify valuable diagnostic and prognostic markers as well as drug targets and treatments for cancer.