Proteogenomic characterization of pancreatic ductal adenocarcinoma

Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, T Mamie Lih, Sara R Savage, Karsten Krug, David J Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Weiming Yang, Jianbo Pan, Bo Wen, Yongchao Dou, Wen Jiang, Yuxing Liao, Zhiao Shi, Nadezhda V Terekhanova, Song Cao, Rita Jui-Hsien Lu, Yize Li, Ruiyang Liu, Houxiang Zhu, Peter Ronning, Yige Wu, Matthew A Wyczalkowski, Hariharan Easwaran, Ludmila Danilova, Arvind Singh Mer, Seungyeul Yoo, Joshua M. Wang, Wenke Liu, Benjamin Haibe-Kains, Mathangi Thiagarajan, Scott D Jewell, Galen Hostetter, Chelsea J Newton, Qing Kay Li, Michael H Roehrl, David Fenyö, Pei Wang, Alexey I Nesvizhskii, DR Mani, Gilbert S Omenn, Emily S Boja, Mehdi Mesri, Ana I Robles, Henry Rodriguez, Oliver F Bathe, Daniel W Chan, Ralph H Hruban, Li Ding, Bing Zhang, Hui Zhang, Mitual Amin, Eunkyung An, Christina Ayad, Thomas Bauer, Chet Birger, Michael J Birrer, Simina M Boca, William Bocik, Melissa Borucki, Shuang Cai, Steven A Carr, Sandra Cerda, Huan Chen, Steven Chen, David Chesla, Arul M Chinnaiyan, Antonio Colaprico, Sandra Cottingham, Magdalena Derejska, Saravana M Dhanasekaran, Marcin J Domagalski, Brian J Druker, Elizabeth Duffy, Maureen A Dyer, Nathan J Edwards, Matthew J Ellis, Jennifer Eschbacher, Alicia Francis, Jesse Francis, Stacey Gabriel, Nikolay Gabrovski, Johanna Gardner, Gad Getz, Michael A Gillette, Charles A Goldthwaite, Pamela Grady, Shuai Guo, Pushpa Hariharan, Tara Hiltke, Barbara Hindenach, Katherine A Hoadley, Jasmine Huang, Corbin D Jones, Karen A Ketchum, Christopher R Kinsinger, Jennifer M Koziak, Katarzyna Kusnierz, Tao Liu, Jiang Long, David Mallery, Sailaja Mareedu, Ronald Matteotti, Nicollette Maunganidze, Peter B McGarvey, Parham Minoo, Oxana V Paklina, Amanda G Paulovich, Samuel H Payne, Olga Potapova, Barbara Pruetz, Liqun Qi, Nancy Roche, Karin D Rodland, Daniel C Rohrer, Eric E Schadt, Alexey V Shabunin, Troy Shelton, Yvonne Shutack, Shilpi Singh, Michael Smith, Richard D Smith, Lori J Sokoll, James Suh, Ratna R Thangudu, Shirley X Tsang, Ki Sung Um, Dana R Valley, Negin Vatanian, Wenyi Wang, George D Wilson, Maciej Wiznerowicz, Zhen Zhang, Grace Zhao
September, 2021
DOI

Abstract

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.

Type
Journal article
Publication
Cell
Joshua M. Wang
Joshua M. Wang
MD/PhD Student

My research interests include deep learning and generative AI for advancing precision healthcare.