Genetic alterations and tumor mutation burden predict chemosensitivity of pancreatic cancer: a retrospective study  

作　　者：Manyi Hu Yiting Xu Yangyang Wang Cao Chen Junjun He Ke Sun Qi Zhang Tingbo Liang 

机构地区：[1]Department of Hepatobiliary and Pancreatic Surgery,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [2]Zhejiang Provincial Key Laboratory of Pancreatic Disease,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [3]Department of Pathology,the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,China [4]Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases,Hangzhou,China [5]The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province,Hangzhou,China [6]Zhejiang University Cancer Center,Hangzhou,China

出　　处：《Journal of Pancreatology》2024年第3期171-180,共10页胰腺病学杂志（英文）

基　　金：This study was supported by the National Key Research&Development Program(No.2020YFA0804300/2020YFA 0804301);the National Natural Science Foundation of China(Nos.U20A20378 and 82273338);the Joint Program of Science and Education Department of State Administration of Traditional Chinese Medicine and Zhejiang Provincial Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-23025).

摘　　要：Background:Chemotherapy stands as a recommended approach for all stages of pancreatic cancer.However,its efficacy stratification remains obscure.Genomic sequencing is extensively applied across diverse diseases.This study aims to explore the potential genomic markers in relation to the decision-making of chemotherapy.Methods:A total of 140 patients with pancreatic cancer were categorized into chemotherapy-first group and adjuvant chemo-therapy group.The genomic alterations were detected from the next-generation sequencing using surgical or fine-needle-biopsy specimens.Chemotherapy response was defined according to objective response based on the RECIST criteria(version 1.1).Results:In the chemotherapy-first group,the patients who harbored higher tumor mutation burden(TMB)levels had significant shorter progress-free survival(PFS)than that with low TMB levels(hazard ratio[HR]=30.362,P=.002).No independent risk factors were found to be correlated with chemoresistance in patients receiving chemotherapy at first(all P>.05).In the adjuvant chemotherapy group,the increased carbohydrate antigen 125(CA125)level of more than 35 U/mL potentially elucidated a shorter period of DFS(HR=3.695,P=.020).Conclusion:Our study indicated that a high level of TMB may predict earlier tumor progression in pancreatic cancer patients received chemotherapy at first.The elevation of CA125 presents itself as a predictive indicator for postoperative chemotherapy patients’tumor recurrence,whereas gene mutations remain unrelated to this phenomenon.

关 键 词：Chemotherapy response Genomic alteration Pancreatic cancer Predictive markers TMB 

分 类 号：R735.9[医药卫生—肿瘤]