Construction and evaluation of a polygenic hazard score for prognostic assessment in localized gastric cancer

作     者：Jing Ni Mengyun Wang Tianpei Wang Caiwang Yan Chuanli Ren Gang Li Yanbing Ding Huizhang Li Lingbin Du Yue Jiang Jiaping Chen Yanong Wang Dazhi Xu Meng Zhu Juncheng Dai Hongxia Ma Zhibin Hu Hongbing Shen Qingyi Wei Guangfu Jin 

作者机构：Department of EpidemiologyCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineChina International Cooperation Center for Environment and Human HealthNanjing Medical UniversityNanjing 211166China Department of Epidemiology and BiostatisticsSchool of Public HealthAnhui Medical UniversityHefei 230032China Cancer InstituteFudan University Shanghai Cancer CenterShanghai 200032China Department of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China Public Health Institute of Gusu SchoolThe Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215006China Department of ImmunologySchool of Basic Medical SciencesNanjing Medical UniversityNanjing 211166China Department of Laboratory MedicineClinical Medical College of Yangzhou UniversityYangzhou 225001China Department of General SurgeryJiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Department of Gastroenterologythe Affiliated Hospital of Yangzhou UniversityYangzhou 225001China Zhejiang Provincial Office for Cancer Prevention and ControlThe Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China Department of Gastric Cancer and Soft Tissue SarcomasFudan University Shanghai Cancer CenterShanghai 200032China Jiangsu Key Laboratory of Molecular and Translational Cancer ResearchJiangsu Cancer HospitalJiangsu Institute of Cancer ResearchThe Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Institute for Precision Cancer Prevention and MedicineGreat Bay Area Institutes of Precision MedicineGuangzhou 511466China Department of Population Health SciencesDuke University School of MedicineDurham 27710United States 

出 版 物：《Fundamental Research》 (自然科学基础研究（英文版）)

年 卷 期：2024年第4卷第5期

页      面：1331-1338页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by National Natural Science Foundation of China(82125033,81872702,82103932,82003534) Natural Science Foundation of Jiangsu Province(BK20200674) 

主　　题：Stomach neoplasm Survival Genome-wide association study Polygenic hazard score Nomogram 

摘      要：To investigate whether genetic variants may provide additional prognostic value to improve the existing clinical staging system for gastric cancer(GC),we performed two genome-wide association studies(GWASs)of GC survival in the Jiangsu(N=1049)and Shanghai(N=1405)*** using a TCGA dataset,we validated genetic markers identified from a meta-analysis of these two Chinese cohorts to determine GC survival-associated ***,we constructed a weighted polygenic hazard score(PHS)and developed a nomogram in combination with clinical *** also evaluated prognostic accuracy with the time-dependent receiver operating characteristic(ROC)curve,net reclassification improvement(NRI)and integrated discrimination improvement(IDI).We identified a single nucleotide polymorphism(SNP)of rs1618332 at 15q15.1 that was associated with the survival of GC patients with a P value of 4.12×10^(-8),and we also found additional 25 SNPs having consistent associations among these two Chinese cohort and TCGA *** PHS derived from these 26 SNPs(PHS-26)was an independent prognostic factor for GC survival(all P0.001).The 5-year AUC of PHS-26 was 0.68,0.66 and 0.67 for Jiangsu,Shanghai and their pooled cohorts,respectively,which increased to 0.80,0.82 and 0.81,correspondingly,after being integrated into a nomogram together with variables of the clinical *** PHS-26 could improve the NRIs by 16.20%,4.90%and 8.70%,respectively,and the IDIs by 11.90%,8.00%and 9.70%,*** 26-SNP based PHS could substantially improve the accuracy of prognostic assessment and might facilitate precision medicine for GC patients.