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Figures S6-S10 from The Proteomic Landscape of Pancreatic Ductal Adenocarcinoma Liver Metastases Identifies Molecular Subtypes and Associations with Clinical Response

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posted on 2023-03-31, 21:31 authored by Henry C.-H. Law, Dragana Lagundžin, Emalie J. Clement, Fangfang Qiao, Zachary S. Wagner, Kimiko L. Krieger, Diane Costanzo-Garvey, Thomas C. Caffrey, Jean L. Grem, Dominick J. DiMaio, Paul M. Grandgenett, Leah M. Cook, Kurt W. Fisher, Fang Yu, Michael A. Hollingsworth, Nicholas T. Woods

Figure S6: Protein expression and gene ontology analysis related to PDAC subtypes. Figure S7: The characterization of Protein Cluster 1. Figure S8: The characterization of Protein Cluster 2. Figure S9: The characterization of Protein Cluster 3. Figure S10: The Kaplan-Meier curves of patients separated based on individual PDAC liver metastasis subtypes.

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ARTICLE ABSTRACT

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

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