학술논문
Proteogenomic characterization of pancreatic ductal adenocarcinoma
Document Type
Report
Author
Cao, Liwei; Huang, Chen; Cui Zhou, Daniel; Hu, Yingwei; Lih, T. Mamie; Savage, Sara R.; Krug, Karsten; Clark, David J.; Schnaubelt, Michael; Chen, Lijun; da Veiga Leprevost, Felipe; Eguez, Rodrigo Vargas; Yang, Weiming; Pan, Jianbo; Wen, Bo; Dou, Yongchao; Jiang, Wen; Liao, Yuxing; Shi, Zhiao; Terekhanova, Nadezhda V.; Cao, Song; Lu, Rita Jui-Hsien; Li, Yize; Liu, Ruiyang; Zhu, Houxiang; Ronning, Peter; Wu, Yige; Wyczalkowski, Matthew A.; Easwaran, Hariharan; Danilova, Ludmila; Mer, Arvind Singh; Yoo, Seungyeul; Wang, Joshua M.; Liu, Wenke; Haibe-Kains, Benjamin; Thiagarajan, Mathangi; Jewell, Scott D.; Hostetter, Galen; Newton, Chelsea J.; Li, Qing Kay; Roehrl, Michael H.; Fenyö, David; Wang, Pei; Nesvizhskii, Alexey I.; Mani, D.R.; Omenn, Gilbert S.; Boja, Emily S.; Mesri, Mehdi; Robles, Ana I.; Rodriguez, Henry; Bathe, Oliver F.; Chan, Daniel W.; Hruban, Ralph H.; Ding, Li; Zhang, Bing; Zhang, Hui; Amin, Mitual; An, Eunkyung; Ayad, Christina; Bauer, Thomas; Birger, Chet; Birrer, Michael J.; Boca, Simina M.; Bocik, William; Borucki, Melissa; Cai, Shuang; Carr, Steven A.; Cerda, Sandra; Chen, Huan; Chen, Steven; Chesla, David; Chinnaiyan, Arul M.; Colaprico, Antonio; Cottingham, Sandra; Derejska, Magdalena; Dhanasekaran, Saravana M.; Domagalski, Marcin J.; Druker, Brian J.; Duffy, Elizabeth; Dyer, Maureen A.; Edwards, Nathan J.; Ellis, Matthew J.; Eschbacher, Jennifer; Francis, Alicia; Francis, Jesse; Gabriel, Stacey; Gabrovski, Nikolay; Gardner, Johanna; Getz, Gad; Gillette, Michael A.; Goldthwaite, Charles A., Jr.; Grady, Pamela; Guo, Shuai; Hariharan, Pushpa; Hiltke, Tara; Hindenach, Barbara; Hoadley, Katherine A.; Huang, Jasmine; Jones, Corbin D.; Ketchum, Karen A.; Kinsinger, Christopher R.; Koziak, Jennifer M.; Kusnierz, Katarzyna; Liu, Tao; Long, Jiang; Mallery, David; Mareedu, Sailaja; Matteotti, Ronald; Maunganidze, Nicollette; McGarvey, Peter B.; Minoo, Parham; Paklina, Oxana V.; Paulovich, Amanda G.; Payne, Samuel H.; Potapova, Olga; Pruetz, Barbara; Qi, Liqun; Roche, Nancy; Rodland, Karin D.; Rohrer, Daniel C.; Schadt, Eric E.; Shabunin, Alexey V.; Shelton, Troy; Shutack, Yvonne; Singh, Shilpi; Smith, Michael; Smith, Richard D.; Sokoll, Lori J.; Suh, James; Thangudu, Ratna R.; Tsang, Shirley X.; Um, Ki Sung; Valley, Dana R.; Vatanian, Negin; Wang, Wenyi; Wilson, George D.; Wiznerowicz, Maciej; Zhang, Zhen; Zhao, Grace
Source
Cell. September 16, 2021, Vol. 184 Issue 19, 5031
Subject
Language
English
ISSN
0092-8674
Abstract
Keywords pancreatic ductal adenocarcinoma; proteogenomics; KRAS; neoplastic cellularity; glycoproteins; kinase inhibitors; immune-cold tumors; endothelial cell; tumor subtyping; CPTAC Highlights * Proteogenomic characterization reveals the functional impact of genomic alterations * Phosphoproteomics uncovers putative therapeutic targets downstream of KRAS * Multiomics links endothelial cell remodeling and glycolysis to immune exclusion * Proteomics and glycoproteomics reveal candidates for early detection or intervention Summary 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.