The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response.

摘要: Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease that can be separated into distinct subtypes based on molecular signatures. Identifying PDAC subtype-specific therapeutic vulnerabilities necessary to develop precision medicine approaches treat PDAC. Experimental Design: A total of 56 liver metastases were obtained from the UNMC Rapid Autopsy Program and analyzed with quantitative proteomics. identified by principal component analysis protein expression profiling. Proteomic further characterized associated clinical information, including but not limited survival analysis, drug treatment response, smoking drinking status. Results: Over 3,960 proteins used delineate four microenvironment subtypes: (i) metabolic; (ii) progenitor-like; (iii) proliferative; (iv) inflammatory. risk factors alcohol tobacco consumption correlate subtype classifications. Enhanced observed in FOLFIRINOX treated metabolic progenitor-like compared proliferative inflammatory subtypes. In addition, TYMP, PDCD6IP, ERAP1, STMN showed significant association patient manner. Gemcitabine-induced alterations proteome identify proteins, such as serine hydroxymethyltransferase 1, resistance. Conclusions: These data demonstrate proteomic signatures unique point opportunities for development improve