KITAHARA Shuji
   Department   Graduate School of Medical Science, Graduate School of Medical Science
   Position   Associate Professor (Fixed Term)
Article types Other
Language English
Peer review Non peer reviewed
Title A tumor microenvironment-based classification of gastric cancer for more effective diagnosis and treatment.
Journal Formal name：Research square
Abbreviation：Res Sq
ISSN code：26935015/26935015
Domestic / ForeginForegin
Volume, Issue, Page pp.0-0
International coauthorship International coauthorship
Author and coauthor Duda Dan, Dima Simona, Sorop Andrei, Kitahara Shuji, Setia Namrata, Chivu-Economescu Mihaela, Matei Lilia, Herlea Vlad, Pechianu Nicolae, Inomata Takenori, Matsui Aya, Khachatryan Anna, Aoki Shuichi, Lauwers Gregory, Popescu Irinel
Publication date 2023/08
Summary With approximately one million diagnosed cases and over 700,000 deaths recorded annually, gastric cancer (GC) is the third most common cause of cancer-related deaths worldwide. GC is a heterogeneous tumor. Thus, optimal management requires biomarkers of prognosis, treatment selection, and treatment response. The Cancer Genome Atlas program sub-classified GC into molecular subtypes, providing a framework for treatment personalization using traditional chemotherapies or biologics. Here, we report a comprehensive study of GC vascular and immune tumor microenvironment (TME)-based on stage and molecular subtypes of the disease and their correlation with outcomes. Using tissues and blood circulating biomarkers and a molecular classification, we identified cancer cell and tumor archetypes, which show that the TME evolves with the disease stage and is a major determinant of prognosis. Moreover, our TME-based subtyping strategy allowed the identification of archetype-specific prognostic biomarkers such as CDH1-mutant GC and circulating IL-6 that provided information beyond and independent of TMN staging, MSI status, and consensus molecular subtyping. The results show that integrating molecular subtyping with TME-specific biomarkers could contribute to improved patient prognostication and may provide a basis for treatment stratification, including for contemporary anti-angiogenesis and immunotherapy approaches.
DOI 10.21203/rs.3.rs-3089359/v1
PMID 37577519