Cholangiocarcinoma combined with biliary obstruction:an exosomal circRNA signature for diagnosis and early recurrence monitoring

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外文摘要：Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches.We present a novel system to monitor CCA using exosomal circular RNA(circRNA)via serum and biliary liquid biopsies.A pilot cohort consisting of patients with CCA-induced biliary obstruction(CCA-BO,n=5)and benign biliary obstruction(BBO,n=5)was used to identify CCA-derived exosomal circRNAs through microarray analysis.This was followed by a discovery cohort(n=20)to further reveal a CCA-specific circRNA complex(hsa-circ-0000367,hsa-circ-0021647,and hsa-circ-0000288)in both bile and serum exosomes.In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness.Diagnostic and prognostic models were established and verified by two independent cohorts(training cohort,n=184;validation cohort,n=105).An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature(Bile-DS,AUROC=0.947,RR=6.05)and serum exosomal circRNA signature(Serum-DS,AUROC=0.861,RR=4.04)compared with conventional CA19-9(AUROC=0.759,RR=2.08).A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score,verified with bile samples(Bile-ERS,C-index=0.783)and serum samples(Serum-ERS,C-index=0.782).These models,combined with other prognostic factors revealed by COX-PH model,enabled the establishment of nomograms for recurrence monitoring of CCA.Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

作者：

Ningyuan Wen、Dingzhong Peng、Xianze Xiong、Geng Liu、Guilin Nie、Yaoqun Wang、Jianrong Xu、Shaofeng Wang、Sishu Yang、Yuan Tian、Bei Li、Jiong Lu、Nansheng Cheng

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作者单位：

Division of Biliary Surgery,Department of General Surgery,West China Hospital,Sichuan University,Chengdu,Sichuan,China

Research Center for Biliary Diseases,West China Hospital,Sichuan University,Chengdu,Sichuan,China

基金：

National Natural Science Foundation of ChinaSichuan Provincial Commission of Health Science ProjectSichuan Science and Technology ProgramSichuan Science and Technology ProgramSichuan Science and Technology ProgramSichuan Science and Technology Program1·3·5 project for disciplines of excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University1·3·5 project for disciplines of excellence,West China Hospital,Sichuan UniversityKey Research and Development Program sponsored by the Ministry of Science and Technology of Chengdu

项目编号：

8200257820PJ0592022YSF00602022YSF01142022NSFSC06802023YFS009420HXFH021ZYJC210492021-YF05-00065-SN

出版年：

2024

DOI：

10.1038/s41392-024-01814-3

信号转导与靶向治疗(英文)

CSTPCD

ISSN：

年,卷(期)：2024.9(6)