期刊
CELL
卷 184, 期 19, 页码 5031-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2021.08.023
关键词
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资金
- National Cancer Institute (NCI) Cinical Proteomic Tumor Analysis Consortium (CPTAC), National Institutes of Health (NIH) [U24CA210955, U24CA210985, U24CA210986, U24CA210954, U24CA 210967, U24CA210972, U24CA210979, U24CA210993, U01CA214114, U01 CA214116, U01CA214125]
- NIH [P30CA008748, P30ES017885]
- Troper Wojcicki Foundation
- Rolfe Pancreatic Cancer Foundation
- Evelyn Grollman Glick Scholar Award
This study conducted comprehensive proteogenomic analysis of PDAC to understand the molecular alterations that drive oncogenesis. Multiple analyses were performed on tissues from patients, providing valuable resources for early detection and identification of therapeutic targets.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.
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