Liu Ruimei, Song Yueqiang, Hua Rulin, Ahmed Shariq, Xie Yunxiao, Lai Cong, Xu Jialu, Li Fuyuan, Li Ying, Li Zhiguang, Wang Yinping, Lv Dekang, Li Qiwei
State Key Laboratory of Genetic Engineering, Human Phenome Institute and School of Life Sciences, Fudan University, Shanghai, 200438 China.
Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 116044 Liaoning China.
Phenomics. 2024 Jun 1;4(4):339-351. doi: 10.1007/s43657-024-00160-2. eCollection 2024 Aug.
Similar clinical manifestations and imaging features between biliary tract inflammatory lesion (BTI) and biliary tract cancer (BTC) pose significant challenges for the management of BTC. To date, the molecular characteristics of the relationship between biliary tract inflammatory lesion and biliary tract cancer remain poorly elucidated. Here, we performed target deep sequencing on 45 BTC patients and 31 BTI patients based on cell-free DNA (cfDNA) in plasma. We characterized the mutational features of 93 cancer-related genes for BTI and BTC. A total of 41% of genes showed concordance between BTI and BTC patients. Mutation burden in cfDNA exhibits a correlation with the levels of cancer antigen 19-9 (CA19-9) ( = 0420) and carcinoembryonic antigen (CEA) ( = 0580). Tumor protein p53 () and low-density lipoprotein receptor-related protein 1B () exhibit the most significant disparity in mutation frequencies between BTC and BTI. Additionally, based on cfDNA, we developed an algorithm, allele fraction variance (AFV), as a supplemental tool for BTC prognosis. Preoperative AFV performed better in predicting prognosis than postoperative one. These findings indicate that genetic mutations in cfDNA accumulate during the progression from BTI to BTC. cfDNA in plasma implies a prognostic value for the BTC.
The online version contains supplementary material available at 10.1007/s43657-024-00160-2.
胆道炎性病变（BTI）和胆道癌（BTC）之间相似的临床表现和影像学特征给BTC的治疗带来了重大挑战。迄今为止，胆道炎性病变与胆道癌之间关系的分子特征仍未得到充分阐明。在此，我们基于血浆中的游离DNA（cfDNA）对45例BTC患者和31例BTI患者进行了靶向深度测序。我们对BTI和BTC的93个癌症相关基因的突变特征进行了表征。共有41%的基因在BTI和BTC患者之间表现出一致性。cfDNA中的突变负担与癌抗原19-9（CA19-9）水平（r = 0.420）和癌胚抗原（CEA）水平（r = 0.580）呈相关性。肿瘤蛋白p53（TP53）和低密度脂蛋白受体相关蛋白1B（LRP1B）在BTC和BTI之间的突变频率差异最为显著。此外，基于cfDNA，我们开发了一种算法，等位基因分数方差（AFV），作为BTC预后的补充工具。术前AFV在预测预后方面比术后表现更好。这些发现表明，cfDNA中的基因突变在从BTI进展到BTC的过程中会积累。血浆中的cfDNA对BTC具有预后价值。
在线版本包含可在10.1007/s43657-024-00160-2获取的补充材料。
