Clinical and molecular heterogeneity associated with tumor sidedness in colorectal liver metastasis: a multicenter propensity cohort study  

作　　者：Yibin Wu Jiamin Zhou Huipeng Wang Guojiu Fang Weiping Zhu Sanjun Cai Lu Wang 

机构地区：[1]Department of Hepatic Surgery,Fudan University Shanghai Cancer Center,Shanghai Medical College,Fudan University,Shanghai,China [2]Department of Oncology,Shanghai Medical College of Fudan University,Fudan University,Shanghai,China [3]Department of General Surgery,Fifth People’s Hospital of Shanghai Fudan University,Shanghai,China [4]Department of General Surgery,Shanghai Fengxian Central Hospital,Shanghai,China [5]Department of Colorectal Surgery,Fudan University Shanghai Cancer Center,Shanghai Medical College,Fudan University,Shanghai,China

出　　处：《Hepatobiliary Surgery and Nutrition》2024年第2期214-228,I0004-I0008,共20页肝胆外科与营养（英文）

基　　金：supported by National Natural Science Foundation of China(81874182,M-0334);Natural Science Foundation of Shanghai(22ZR1413300);National Science and Technology Major Project(2017ZX10203204-007-004);Shanghai Municipal Health Bureau(201940043);Shanghai Hospital Development Center(SHDC12019X19).

摘　　要：Background:Colorectal liver metastasis(CRLM)exhibits highly heterogeneity,with clinically and molecularly defined subgroups that differ in their prognosis.The aim of this study is to explore whether left-sided tumors is clinically and gnomically distinct from right-sided tumors in CRLM.Methods:This retrospective study included 1,307 patients who underwent primary tumor and metastases resection at three academic centers in China from January 1,2012,to December 31,2020.Propensity score matching with 1:1 ratio matching was performed.The prognostic impact of tumor sidedness was determined after stratifying by the KRAS mutational status.Moreover,whole-exome sequencing(WES)of 200 liver tumor tissues were performed to describe the heterogeneity across the analysis of somatic and germline profiles.Results:The median follow-up was 68 months.Matching yielded 481 pairs of patients.Compared to right-sided CRLM,left-sided patients experienced with better 5-year overall survival(OS)in surgery responsiveness,with a 14.6 lower risk of death[hazard ratio(HR),1.36,95%confidence interval(CI),1.10-1.69,P=0.004].Interaction between tumor sidedness and KRAS status was statistically significant:left-sidedness was associated with better prognosis among KRAS wild-type patients(HR 1.71;95%CI:1.20-2.45;P=0.003),but not among KRAS mutated-type patients.Integrated molecular analyses showed that right-sided tumors more frequently harbored TP53,APC,KRAS,and BRAF alterations,and identified a critical role of KRAS mutation in correlation with their survival differences.Higher pathogenic germline variants were identified in the right-sided tumors compared with left-sided tumors(29.3%vs.15.5%,P=0.03).Conclusions:We demonstrated that the prognostic impacts of tumor sidedness in CRLM is restricted patients with KRAS wild-type tumors.Tumor sidedness displays considerable clinical and molecular heterogeneity that may associate with their therapy benefits and prognosis.

关 键 词：Colorectal liver metastasis(CRLM) tumor sidedness KRAS mutational status somatic mutation germline mutation germline mutation 

分 类 号：R735.34[医药卫生—肿瘤]