Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Department of Gastrointestinal Surgery, Ningbo No.2 Hospital, Ningbo, Zhejiang, 315010, China.
Genome Med. 2024 Jun 7;16(1):79. doi: 10.1186/s13073-024-01352-1.
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.
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.
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.
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.
This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.
胃癌是第五大常见癌症类型。大多数患者在晚期诊断，预后较差。对于降低相关死亡率，非常需要一种用于检测早期胃癌的非侵入性检测方法。
我们收集了一个前瞻性研究队列，其中包括 110 例 I-II 期胃癌患者和 139 名非癌症个体。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游离 DNA（cfDNA）特征，即片段大小模式、拷贝数变异、核小体覆盖模式和单核苷酸替换。根据这些差异图谱，我们开发了一个集成模型来检测胃癌信号。此外，我们在内部的 73 例胃癌患者和 94 例非癌症个体的第一个验证队列以及 47 例胃癌患者和 49 例非癌症个体的独立第二个验证队列中验证了该检测方法。此外，我们通过蒙特卡罗模拟评估了该检测方法在 100,000 例筛查人群中的应用。
我们的基于 cfDNA 的检测方法可以在研究队列中区分早期胃癌与非癌症，AUROC 为 0.962（95%CI：0.942-0.982），在第一个验证队列中为 0.972（95%CI：0.953-0.992），在第二个验证队列中为 0.937（95%CI：0.890-0.983）。在研究队列中，该模型的特异性为 92.1%（128/139），敏感性为 88.2%（97/110）。在第一个验证队列中，91.5%（86/94）的非癌症个体和 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）的非癌症个体和 87.2%（41/47）的胃癌患者被准确分类。
我们引入了一种使用 cfDNA 特征的多个维度的液体活检检测方法，可准确识别早期胃癌与非癌性疾病。作为一种具有成本效益的非侵入性方法，它可能为胃癌的早期检测提供广泛的人群效益。
本研究于 2022 年 3 月 7 日在 ClinicalTrials.gov 上注册，标识符为 NCT05269056。
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