Proteome alterations in pancreatic ductal adenocarcinoma

Proteins are the essential functional biomolecules profoundly implicated in all aspects of pancreatic tumorigenesis and its progression. While common genomic factors, such as KRAS, TP53, SMAD4, and CDKN2A have been well recognized in association of pancreatic ductal adenocarcinoma (PDAC), our understanding of functional changes at the proteome level merits further investigation. Malignance associated proteome alterations can be attributed to the convoluted outcomes from genetic, epigenetic and environmental factors in initiating and progressing PDAC, and may reflect on changes in protein expressional level, structure, localization, as well as post-translational modifications (PTMs) status. The study of localized or systemic proteome alterations in PDAC, as well as its precursor lesions, such as pancreatic intraepithelial neoplasia (PanIN) and mucinous pancreatic cystic neoplasm, would provide unique perspectives in elucidating functional molecular events underlying PDAC. While efforts have been made, challenges still exist to comprehensively integrate much of the proteomic discovery to the perspectives gained from genomic studies in the context of biomarker discovery. Novel approaches and data from well-defined longitudinal clinical studies and experimental models are needed to facilitate the study of PDAC and precursor lesions for early detection and intervention.