Abstract 2285: Mass spectrometry-based proteomics profiling reveals differential proteome composition in tumor and normal tissues, with implications for normalization

Abstract

Abstract The composition of the proteome varies significantly across different tissues and disease states creating a challenge of how best to compare expression levels of each protein across these tissue types. Traditionally, a median approach to normalization has been used, but this could obscure meaningful biological differences between tissues. Here, we present a quantitative proteomic study analyzing proteome composition across tumor and normal tissues in order to assess normalization methods. Human proteomes covering 7 cancer indications (244 samples) and 12 normal tissue organs (370 samples) were analyzed by data-independent acquisition mass spectrometry. On average, over 8,000 proteins were quantified across the study cohorts. Comparison of proteomes revealed an average of 11.4% higher protein identification in tumors compared to matched normal tissues (6 tumor types all p<0.003). Tissue origin strongly influenced proteome composition, most notably in bone marrow, while cancer tissues displayed less proteomic composition variation than normal tissues. Compared to global median normalization, riBAQ and tissue-specific quantile normalization reduced technical variances while maintaining biological differences between tissue types. By revealing tissue-specific proteome signatures as well as systemic proteomic alterations in tumors, this study lays the groundwork for appropriate comparative approaches accounting for tissue origins, and establishes a framework for discovery of tissue-specific biomarkers, which may facilitate the development of novel diagnostic and prognostic tests, and guide therapeutic interventions for cancer. Citation Format: Ying Zheng, Lindsay Olita, McIver Nivens, Abby Chiang, Shreya Ahuja, Matthew Glover, John Bullen, Elaine Hurt, Wenyan Zhong. Mass spectrometry-based proteomics profiling reveals differential proteome composition in tumor and normal tissues, with implications for normalization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2285.