Identification of collagen subtypes of gastric cancer for distinguishing patient prognosis and therapeutic response  

作　　者：Di Wang Jing Zhang Jianchao Wang Zhonglin Cai Shanfeng Jin Gang Chen 

机构地区：[1]Department of Molecular Pathology,Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital,Fuzhou,China [2]Department of Pathology,Clinical Oncology School of Fujian Medical University,Fujian Cancer Hospital,Fuzhou,China [3]Department of Urology,Gongli Hospital of Shanghai Pudong New Area,Shanghai,China

出　　处：《Cancer Innovation》2024年第4期87-102,共16页肿瘤学创新（英文）

基　　金：Science and Technology Program of Fujian Province of China,Grant/Award Number:2019YZ016006;Scientific Research Foundation of Fujian Cancer Hospital,Grant/Award Number:2022YNG08。

摘　　要：Background:Gastric cancer is a highly heterogeneous disease,presenting a major obstacle to personalized treatment.Effective markers of the immune checkpoint blockade response are needed for precise patient classification.We,therefore,divided patients with gastric cancer according to collagen gene expression to indicate their prognosis and treatment response.Methods:We collected data for 1250 patients with gastric cancer from four cohorts.For the TCGA‐STAD cohort,we used consensus clustering to stratify patients based on expression levels of 44 collagen genes and compared the prognosis and clinical characteristics between collagen subtypes.We then identified distinct transcriptomic and genetic alteration signatures for the subtypes.We analyzed the associations of collagen subtypes with the responses to chemotherapy,immunotherapy,and targeted therapy.We also established a platform‐independent collagen‐subtype predictor.We verified the findings in three validation cohorts(GSE84433,GSE62254,and GSE15459)and compared the collagen subtyping method with other molecular subtyping methods.Results:We identified two subtypes of gastric adenocarcinoma:a highexpression collagen subtype(CS‐H)and a low‐expression collagen subtype(CS‐L).Collagen subtype was an independent prognostic factor,with better overall survival in the CS‐L subgroup.The inflammatory response,angiogenesis,and phosphoinositide 3‐kinase(PI3K)/Akt pathways were transcriptionally active in the CS‐H subtype,while DNA repair activity was significantly greater in the CS‐L subtype.PIK3CA was frequently amplified in the CS‐H subtype,while PIK3C2A,PIK3C2G,and PIK3R1 were frequently deleted in the CS‐L subtype.CS‐H subtype tumors were more sensitive to fluorouracil,while CS‐L subtype tumors were more sensitive to immune checkpoint blockade.CS‐L subtype was predicted to be more sensitive to HER2‐targeted drugs,and CS‐H subtype was predicted to be more sensitive to vascular endothelial growth factor and PI3K pathway‐targeting drugs.Co

关 键 词：BIOMARKER cancer classification COLLAGEN gastric cancer phosphatidylinositol 3‐kinase 

分 类 号：R730[医药卫生—肿瘤]