背景:胆道癌(BTC)的诊断在临床实践中具有挑战性。我们进行了一项前瞻性研究,以评估血浆拷贝数变异(CNV)测定在诊断BTC中的价值。
方法:纳入47例可疑胆道病变的初治患者。在入院时收集血浆样品。通过低覆盖率全基因组测序分析无细胞DNA,然后通过定制的生物信息学工作流程进行CNV分析,即超敏染色体非整倍体检测器。
结果:29例患者病理诊断为BTC,包括8例胆囊癌(GBC)和21例胆管癌(CC)。与良性患者相比,癌症患者的CNV信号更多(26/29vs.2/18,P<0.001)。最频繁的拷贝数增益是chr3q(7/29)和chr8q(6/29)。最常见的拷贝数损失是chr7p(6/29),chr17p(6/29),和chr19p(6/29)。血浆CNV检测诊断BTC的敏感性和特异性分别为89.7%和88.9%,分别。对于CA19-9(截止:37U/ml),敏感性为58.6%,特异性为72.2%.CNV检测的诊断准确性显著优于CA19-9(AUC0.91vs.0.62,P=0.004)。与单独的CA19-9相比,在CA19-9中添加CNV谱增加了诊断GBC的敏感性(75.0%vs.25.0%)和CC(100%与52.4%)。较高的CNV负荷也与总生存率降低相关(危险比=4.32,95%CI2.06-9.08,P=0.033)。
结论:我们的结果表明,BTC具有丰富的血浆CNV信号,和他们的检测可能是有用的诊断BTC。
BACKGROUND: The diagnosis of biliary tract cancer (BTC) is challenging in clinical practice. We performed a prospective study to evaluate the value of plasma copy number variation (CNV) assays in diagnosing BTC.
METHODS: 47 treatment-naïve patients with suspicious biliary lesions were recruited. Plasma samples were collected at admission. Cell-free DNA was analyzed by low coverage whole genome sequencing, followed by CNV analyses via a customized bioinformatics workflow, namely the ultrasensitive chromosomal aneuploidy detector.
RESULTS: 29 patients were pathologically diagnosed as BTC, including 8 gallbladder cancers (GBCs) and 21 cholangiocarcinomas (CCs). Cancer patients had more CNV signals as compared with benign patients (26/29 vs. 2/18, P < 0.001). The most frequent copy number gains were chr3q (7/29) and chr8q (6/29). The most frequent copy number losses were chr7p (6/29), chr17p (6/29), and chr19p (6/29). The sensitivity and specificity of plasma CNV assays in diagnosing BTC were 89.7% and 88.9%, respectively. For CA 19-9 (cutoff: 37 U/ml), the sensitivity was 58.6% and the specificity was 72.2%. The diagnostic accuracy of CNV assays significantly outperformed CA 19-9 (AUC 0.91 vs. 0.62, P = 0.004). Compared with CA 19-9 alone, the adding of CNV profiles to CA 19-9 increased the sensitivity in diagnosing GBC (75.0% vs. 25.0%) and CC (100% vs. 52.4%). Higher CNV burden was also associated with decreased overall survival (Hazard ratio = 4.32, 95% CI 2.06-9.08, P = 0.033).
CONCLUSIONS: Our results suggest that BTC harbors rich plasma CNV signals, and their assays might be useful for diagnosing BTC.