Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, WA, 98195, USA.
Cancer Lett. 2020 Jan 28;469:429-436. doi: 10.1016/j.canlet.2019.11.020. Epub 2019 Nov 14.
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.
蛋白质是在胰腺癌发生和进展的各个方面都有深刻影响的重要功能生物分子。虽然常见的基因组因素，如 KRAS、TP53、SMAD4 和 CDKN2A，已被广泛认为与胰腺导管腺癌（PDAC）相关，但我们对蛋白质组水平的功能变化的理解值得进一步研究。与恶性相关的蛋白质组改变可以归因于遗传、表观遗传和环境因素在启动和进展 PDAC 中的复杂结果，并且可能反映在蛋白质表达水平、结构、定位以及翻译后修饰（PTMs）状态的变化上。对 PDAC 及其前体病变（如胰腺上皮内瘤变（PanIN）和黏液性胰腺囊性肿瘤）的局部或系统性蛋白质组改变的研究，以及从基因组研究中获得的观点，将为阐明 PDAC 背后的功能分子事件提供独特的视角。虽然已经做出了努力，但在将蛋白质组学发现全面整合到基于基因组研究的生物标志物发现的观点方面仍然存在挑战。需要来自明确的纵向临床研究和实验模型的新方法和数据来促进 PDAC 和前体病变的研究，以实现早期检测和干预。
