Clinically conserved genomic subtypes of gastric adenocarcinoma

Molecular Cancer

Research

Joo Kyung Noh¹  Young-Gyu Eun²  Shumei Song³  Jaffer A. Ajani³  Eui Hyun Kim⁴  Seon Rang Woo⁵  Moonkyoo Kong⁶  Sang-Hee Kang⁷  Deok Hwa Nam⁸  Bo Hwa Sohn⁸  Ju-Seog Lee⁸  Yun Seong Jeong⁸  Sun Young Yim⁹  Jeeyun Lee^1,10  Sung Hwan Lee^1,11  Sang Cheul Oh^1,12  Hyun-Sung Lee^1,13  Hee-Jin Jang^1,13 

[1]Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea

[2]Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea

[3]Department of Otolaryngology - Head and Neck Surgery, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea

[4]Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

[5]Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea

[6]Department of Otolaryngology - Head and Neck Surgery, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea

[7]Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea

[8]Department of Surgery, Korea University Guro Hospital, Seoul, Korea

[9]Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1058, 77030, Houston, TX, USA

[10]Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

[11]Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

[12]Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Yonsei University College of Medicine, Seoul, Korea

[13]Division of Hepatobiliary and Pancreas, Department of Surgery, CHA Bundang Medical Center, CHA University, Pocheon, Korea

[14]Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea

[15]Systems Onco-Immunology Laboratory, David J. Sugarbaker Division of Thoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA

关键词: Gastric cancer;    Consensus subtype;    Clinical subtypes;    Stem cells;    Cancer immune activity;    Radiation therapy;   

DOI  :  10.1186/s12943-023-01796-w

 received in 2023-02-25, accepted in 2023-05-31,  发布年份 2023

来源: Springer

【 摘 要 】

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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