Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

IF 10.4 1区生物学 Q1 GENETICS & HEREDITY

Genome Medicine Pub Date : 2024-06-07 DOI:10.1186/s13073-024-01352-1

Pengfei Yu, Ping Chen, Min Wu, Guangyu Ding, Hua Bao, Yian Du, Zhiyuan Xu, Litao Yang, Jingquan Fang, Xingmao Huang, Qian Lai, Jia Wei, Junrong Yan, Shanshan Yang, Peng He, Xue Wu, Yang Shao, Dan Su, Xiangdong Cheng

{"title":"Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.","authors":"Pengfei Yu, Ping Chen, Min Wu, Guangyu Ding, Hua Bao, Yian Du, Zhiyuan Xu, Litao Yang, Jingquan Fang, Xingmao Huang, Qian Lai, Jia Wei, Junrong Yan, Shanshan Yang, Peng He, Xue Wu, Yang Shao, Dan Su, Xiangdong Cheng","doi":"10.1186/s13073-024-01352-1","DOIUrl":null,"url":null,"abstract":"Background: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.Methods: We collected a prospective study cohort of 110 stage I-II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation.Results: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942-0.982) in the study cohort, 0.972 (95% CI: 0.953-0.992) in the first validation cohort and 0.937 (95% CI: 0.890-0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified.Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer.Trial registration: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":null,"pages":null},"PeriodicalIF":10.4000,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157707/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome Medicine","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13073-024-01352-1","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality.

Methods: We collected a prospective study cohort of 110 stage I-II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation.

Results: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942-0.982) in the study cohort, 0.972 (95% CI: 0.953-0.992) in the first validation cohort and 0.937 (95% CI: 0.890-0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified.

Conclusions: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer.

Trial registration: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

查看原文本刊更多论文

基于无细胞 DNA 的多维液体活检技术，用于敏感地早期检测胃癌。

背景：胃癌是第五大常见癌症类型：胃癌是第五大常见癌症类型。大多数患者确诊时已是晚期，预后较差。为降低相关死亡率，非常需要一种非侵入性检测方法来检测早期胃癌：方法：我们收集了 110 名 I-II 期胃癌患者和 139 名非癌症患者的前瞻性研究队列。我们对血浆样本进行了全基因组测序，并分析了四种类型的无细胞 DNA（cfDNA）特征：片段大小模式、拷贝数变异、核小体覆盖模式和单核苷酸置换。利用这些差异特征，我们建立了一个检测胃癌信号的集合模型。此外，我们还在由 73 名胃癌患者和 94 名非癌症患者组成的内部第一验证队列以及由 47 名胃癌患者和 49 名非癌症患者组成的独立第二验证队列中验证了该检测方法。此外，我们还通过蒙特卡洛模拟对假设的 10 万筛查人群进行了评估：结果：我们基于 cfDNA 的检测方法可以区分早期胃癌和非癌症，研究队列的 AUROC 为 0.962（95% CI：0.942-0.982），第一个验证队列的 AUROC 为 0.972（95% CI：0.953-0.992），第二个验证队列的 AUROC 为 0.937（95% CI：0.890-0.983）。该模型在研究队列中的特异性为 92.1%（128/139），灵敏度为 88.2%（97/110）。在第一个验证队列中，91.5%（86/94）的非癌症患者和 91.8%（67/73）的胃癌患者被正确识别。在第二个验证队列中，89.8%（44/49）的非癌症患者和 87.2%（41/47）的胃癌患者被准确分类：我们引入了一种利用多维度的 cfDNA 特征进行液体活检的检测方法，它能准确地从非癌症病症中识别出早期胃癌。作为一种具有成本效益的非侵入性方法，它可为胃癌的早期检测提供全民受益：本研究于2022年3月7日在ClinicalTrials.gov上注册，标识符为NCT05269056。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Genome Medicine GENETICS & HEREDITY-

CiteScore

20.80

自引率

0.80%

发文量

128

审稿时长

6-12 weeks

期刊介绍： Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.