胆汁多基因液体活检对确定胆管癌驱动基因的作用。

IF 5.7 2区 医学 Q1 Medicine Cancer Science Pub Date : 2024-10-08 DOI:10.1111/cas.16365
Shin Ito, Mika Ando, Shuichi Aoki, Satoshi Soma, Jie Zhang, Naohiro Hirano, Ryosuke Kashiwagi, Keigo Murakami, Shingo Yoshimachi, Hideaki Sato, Akiko Kusaka, Masahiro Iseki, Koetsu Inoue, Masamichi Mizuma, Kiyoshi Kume, Kei Nakagawa, Atsushi Masamune, Naoki Asano, Jun Yasuda, Michiaki Unno
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引用次数: 0

摘要

液体活检(LB)是以最小侵袭获取肿瘤衍生材料的重要工具。研究表明,胆汁中的游离核酸含量远高于血浆,而且可以通过内窥镜手术收集。因此,胆汁作为胆管癌的肿瘤衍生无细胞 DNA(cfDNA)来源具有很大的潜力。在本研究中,我们发现血浆 LB 的多基因面板也可应用于胆汁 cfDNA,以比较其他来源(血浆和相应患者的肿瘤组织)的驱动基因突变检测。我们从 24 例胆道癌症患者的胆汁中采集了 cfDNA 样本。其中包括 17 例胆管癌、3 例胰腺癌、2 例胰腺癌、1 例导管内乳头状黏液癌和 1 例胰岛素瘤。在手术切除前,我们从相应的患者处获得了 17 份血浆样本,并对其进行了 LiquidPlex 多基因面板 LB 系统检测。我们采用机器学习方法,在LiquidPlex高保真分析软件包预过滤的变异调用中对可能的肿瘤衍生变异进行分类。在 17 例胆管癌中,我们利用 LiquidPlex 系统检测到了 10 例胆汁中的癌症驱动基因突变。在用这种方法检测的胆道癌病例中,分别有13例(54%)和4例(17%)在胆汁和血浆cfDNA中检测到阳性的癌症驱动基因突变。这些结果表明,与血浆相比,胆汁是进行胆道癌多基因面板分析的更可靠的 LB 来源。
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Usefulness of multigene liquid biopsy of bile for identifying driver genes of biliary duct cancers.

Liquid biopsy (LB) is an essential tool for obtaining tumor-derived materials with minimum invasion. Bile has been shown to contain much higher free nucleic acid levels than blood plasma and can be collected through endoscopic procedures. Therefore, bile possesses high potential as a source of tumor derived cell-free DNA (cfDNA) for bile duct cancers. In this study, we show that a multigene panel for plasma LB can also be applied to bile cfDNA for comparing driver gene mutation detection in other sources (plasma and tumor tissues of the corresponding patients). We collected cfDNA samples from the bile of 24 biliary tract cancer cases. These included 17 cholangiocarcinomas, three ampullary carcinoma, two pancreatic cancers, one intraductal papillary mucinous carcinoma, and one insulinoma. Seventeen plasma samples were obtained from the corresponding patients before surgical resection and subjected to the LiquidPlex multigene panel LB system. We applied a machine learning approach to classify possible tumor-derived variants among the prefiltered variant calls by a LiquidPlex analytical package with high fidelity. Among the 17 cholangiocarcinomas, we could detect cancer driver mutations in the bile of 10 cases using the LiquidPlex system. Of the biliary tract cancer cases examined with this method, 13 (54%) and 4 (17%) resulted in positive cancer driver mutation detection in the bile and plasma cfDNAs, respectively. These results suggest that bile is a more reliable source for LB than plasma for multigene panel analyses of biliary tract cancers.

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来源期刊
Cancer Science
Cancer Science ONCOLOGY-
CiteScore
9.90
自引率
3.50%
发文量
406
审稿时长
17 weeks
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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