Proteogenomic landscape of gastric adenocarcinoma peritoneal metastases

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

doi:10.1016/j.isci.2023.106913

Proteogenomic landscape of gastric adenocarcinoma peritoneal metastases

iScience. 2023 May 19;26(6):106913. doi: 10.1016/j.isci.2023.106913. eCollection 2023 Jun 16.

Authors

Shuangtao Zhao¹, Ruiping Wang¹, Shumei Song², Dapeng Hao¹, Guangchun Han¹, Xingzhi Song¹, Jianhua Zhang¹, Melissa Pool Pizzi², Namita Shanbhag², Andrew Futreal¹, Brian Badgwell³, Kazuto Harada², George Calin⁴, Jody Vykoukal⁵, Chuan-Yih Yu⁵, Hiroyuki Katayama⁵, Samir M Hanash⁵, Linghua Wang¹, Jaffer A Ajani²

Affiliations

¹ Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁵ Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.