Proteogenomic characterization of pancreatic ductal adenocarcinoma.

Authors

Liwei Cao
Chen Huang
Daniel Cui Zhou
Yingwei Hu
T Mamie Lih
Sara R Savage
Karsten Krug
David J Clark
Michael Schnaubelt
Lijun Chen
George D. Wilson, Beaumont Health
Mitual Amin, Beaumont Health
Barbara Pruetz, Beaumont Health

Document Type

Article

Publication Date

9-16-2021

Publication Title

Cell

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.

Volume

184

Issue

19

First Page

5031

Last Page

5052

Recommended Citation

Cao L, Huang C, Cui Zhou D, Hu Y, Lih TM, Savage SR, Krug K, Clark DJ, Schnaubelt M, Chen L, da Veiga Leprevost F, Eguez RV, Yang W, Pan J, Wen B, Dou Y, Jiang W, Liao Y, Shi Z, Terekhanova NV, Cao S, Lu RJ, Li Y, Liu R, Zhu H, Ronning P, Wu Y, Wyczalkowski MA, Easwaran H, Danilova L, Mer AS, Yoo S, Wang JM, Liu W, Haibe-Kains B, Thiagarajan M, Jewell SD, Hostetter G, Newton CJ, Li QK, Roehrl MH, Fenyö D, Wang P, Nesvizhskii AI, Mani DR, Omenn GS, Boja ES, Mesri M, Robles AI, Rodriguez H, Bathe OF, Chan DW, Hruban RH, Ding L, Zhang B, Zhang H; Clinical Proteomic Tumor Analysis Consortium. Proteogenomic characterization of pancreatic ductal adenocarcinoma. Cell. 2021 Sep 16;184(19):5031-5052.e26. doi: 10.1016/j.cell.2021.08.023. PMID: 34534465; PMCID: PMC8654574.

DOI

10.1016/j.cell.2021.08.023

ISSN

1097-4172

PubMed ID

34534465