Proteogenomic Landscape of Gastric Adenocarcinoma Peritoneal Metastases

Authors

Shuangtao Zhao
Ruiping Wang
Shumei Song
Dapeng Hao
Guangchun Han
Xingzhi Song
Jianhua Zhang
Melissa Pool Pizzi
Namita Shanbhag
Andrew Futreal
Brian Badgwell
Kazuto Harada
George Calin
Jody Vykoukal
Chuan-Yih Yu
Hiroyuki Katayama
Samir M Hanash
Linghua Wang
Jaffer A Ajani

Publication Date

6-16-2023

Journal

iScience

Abstract

Advanced gastric adenocarcinoma (GAC) often leads to peritoneal carcinomatosis (PC) and is associated with very poor outcome. Here we report the comprehensive proteogenomic study of ascites derived cells from a prospective GAC cohort (n = 26 patients with peritoneal carcinomatosis, PC). A total of 16,449 proteins were detected from whole cell extracts (TCEs). Unsupervised hierarchical clustering resulted in three distinct groups that reflected extent of enrichment in tumor cells. Integrated analysis revealed enriched biological pathways and notably, some druggable targets (cancer-testis antigens, kinases, and receptors) that could be exploited to develop effective therapies and/or tumor stratifications. Systematic comparison of expression levels of proteins and mRNAs revealed special expression patterns of key therapeutics target notably high mRNA and low protein expression of HAVCR2 (TIM-3), and low mRNA but high protein expression of cancer-testis antigens CTAGE1 and CTNNA2. These results inform strategies to target GAC vulnerabilities.

Keywords

Biological sciences, Cancer, Genomics, Proteomics

Comments

Supplementary Materials

PMID: 37305699