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

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

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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.

Original language	English (US)
Article number	106913
Journal	iScience
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/j.isci.2023.106913
State	Published - Jun 16 2023

Keywords

Biological sciences
Cancer
Genomics
Proteomics

ASJC Scopus subject areas

General

MD Anderson CCSG core facilities

Tissue Biospecimen and Pathology Resource
Advanced Technology Genomics Core
Functional Proteomics Reverse Phase Protein Array Core
Bioinformatics Shared Resource

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10.1016/j.isci.2023.106913

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Zhao, S., Wang, R., Song, S., Hao, D., Han, G., Song, X., Zhang, J., Pizzi, M. P., Shanbhag, N., Futreal, A., Badgwell, B., Harada, K., Calin, G., Vykoukal, J., Yu, C. Y., Katayama, H., Hanash, S. M., Wang, L., & Ajani, J. A. (2023). Proteogenomic landscape of gastric adenocarcinoma peritoneal metastases. iScience, 26(6), Article 106913. https://doi.org/10.1016/j.isci.2023.106913

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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",

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

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month = jun,

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doi = "10.1016/j.isci.2023.106913",

language = "English (US)",

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AU - Zhao, Shuangtao

AU - Wang, Ruiping

AU - Song, Shumei

AU - Hao, Dapeng

AU - Han, Guangchun

AU - Song, Xingzhi

AU - Zhang, Jianhua

AU - Pizzi, Melissa Pool

AU - Shanbhag, Namita

AU - Futreal, Andrew

AU - Badgwell, Brian

AU - Harada, Kazuto

AU - Calin, George

AU - Vykoukal, Jody

AU - Yu, Chuan Yih

AU - Katayama, Hiroyuki

AU - Hanash, Samir M.

AU - Wang, Linghua

AU - Ajani, Jaffer A.

PY - 2023/6/16

Y1 - 2023/6/16

N2 - 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.

AB - 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.

KW - Biological sciences

KW - Cancer

KW - Genomics

KW - Proteomics

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Proteogenomic landscape of gastric adenocarcinoma peritoneal metastases

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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