Reverse engineering a predictive signature characterized by proliferation,DNA damage,and immune escape from stage I lung adenocarcinoma recurrence

查看全文 作　　者：Jiannan [1]Yao;Xinying [2]Xue;Dongfeng [3,4]Qu;C.Benedikt [5]Westphalen;Yang [1]Ge;Liyang [6]Zhang;Manyu [1]Li;Tianbo [1]Gao;Parthasarathy [3,4]Chandrakesan;Kenneth [7]J.Vega;Jun [8,9]Peng;Guangyu [1]An;Nathaniel [8,9]Weygant

机构地区：[1]Department of Oncology,Beijing Chao-Yang Hospital,Capital Medical University,Beijing 100020,China;[2]Department of Respiratory and Critical Care Medicine,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;[3]Department of Medicine,The University of Oklahoma Health Sciences Center,Oklahoma City,73103,OK,USA;[4]Stephenson Cancer Center,Oklahoma City,73104,OK,USA;[5]Comprehensive Cancer Center Munich&Department of Medicine III,Ludwig Maximilian University of Munich,81377,Munich,Germany;[6]Xiangya Hospital,Central South University,Changsha 410008,China;[7]Division of Gastroenterology and Hepatology,Augusta University,Augusta,30912,GA,USA;[8]Academy of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;[9]Fujian Key Laboratory of Integrative Medicine in Geriatrics,Fuzhou 350122,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2020年第52卷第6期,共16页

基　　金：the grant from Beijing Municipal Administration of Hospitals,Incubating Program(No.PX 2020016). 摘　　要：Identifying early-stage cancer patients at risk for progression is a major goal of biomarker research.This report describes a novel 19-gene signature(19-GCS)that predicts stage I lung adenocarcinoma(LAC)recurrence and responseto therapy and performs comparably in pancreatic adenocarcinoma(PAC),which shares LAC molecular traits.Kaplan-Meier,Cox regression,and cross-validation analyses were used to build the signature from training,test,and validation sets comprising 831 stage I LAC transcriptomes from multiple independent data sets.A statistical analysis was performed using the R Ianguage.Pathway and gene set enrichment were used to identify underlying mechanisms.19-GCS strongly predicts overall survival and recurrence-free survival in stage I LAC(P=0.002 and P<0.001,respectively)and in stage l-ll PAC(P<0.0001 and Pv0.0005,respectively).A multivariate cox regression analysis demonstrated the independence of 19-GCS from significant clinical factors.Pathway analyses revealed that 19-GCS high-risk LAC and PAC tumors are characterized by increased proliferation,enhanced sternness,DNA repair deficiency,and compromised MHC class I and II antigen presentation along with decreased immune infiltration.Importantly,high-risk LAC patients do not appear to benefit from adjuvant cisplatin while PAC patients derive additi onal ben efit from FOLFIRINOX compared with gemcitabi ne-based regimens.Whe n validated prospectively,this proof-of-c on cept biomarker may con tribute to tailoring treatment,recurrence reduction,and survival improvements in early-stage lung and pancreatic cancers. 关键词：lung adenocarcinoma pancreatic adenocarcinoma BIOMARKER prognosis immunity

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Reverse engineering a predictive signature characterized by proliferation,DNA damage,and immune escape from stage I lung adenocarcinoma recurrence

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