Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Division of Surgical Oncology, National University Cancer Institute, Singapore.
Gut. 2021 May;70(5):829-837. doi: 10.1136/gutjnl-2020-322065. Epub 2020 Oct 7.
An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population.
We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea. Biomarker discovery and verification phases were done through comprehensive serum miRNA profiling and multivariant analysis of 578 miRNA candidates in retrospective cohorts of 682 subjects. A clinical assay was developed and validated in a prospective cohort of 4566 symptomatic subjects who underwent endoscopy. Assay performance was confirmed with histological diagnosis and compared with (HP) serology, serum pepsinogens (PGs), 'ABC' method, carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). Cost-effectiveness was analysed using a Markov decision model.
We developed a clinical assay for detection of gastric cancer based on a 12-miRNA biomarker panel. The 12-miRNA panel had area under the curve (AUC)=0.93 (95% CI 0.90 to 0.95) and AUC=0.92 (95% CI 0.88 to 0.96) in the discovery and verification cohorts, respectively. In the prospective study, overall sensitivity was 87.0% (95% CI 79.4% to 92.5%) at specificity of 68.4% (95% CI 67.0% to 69.8%). AUC was 0.848 (95% CI 0.81 to 0.88), higher than HP serology (0.635), PG 1/2 ratio (0.641), PG index (0.576), ABC method (0.647), CEA (0.576) and CA19-9 (0.595). The number needed to screen is 489 annually. It is cost-effective for mass screening relative to current practice (incremental cost-effectiveness ratio=US$44 531/quality-of-life year).
We developed and validated a serum 12-miRNA biomarker assay, which may be a cost-effective risk assessment for gastric cancer.
This study is registered with ClinicalTrials.gov (Registration number: NCT04329299).
目前需要一种非侵入性生物标志物检测方法来辅助胃癌的诊断。本研究旨在开发一种用于鉴定高风险人群中各期胃癌患者的血清 microRNA（miRNA）组合。
本研究共纳入了来自新加坡和韩国的 5248 名受试者，分三个阶段、多中心进行。通过对 578 个 miRNA 候选物进行综合血清 miRNA 谱分析和多变量分析，对 682 名受试者的回顾性队列进行了生物标志物发现和验证阶段。在对 4566 名有症状并接受内镜检查的受试者进行前瞻性队列研究中，开发并验证了临床检测方法。通过组织学诊断和与（HP）血清学、血清胃蛋白酶原（PG）、“ABC”方法、癌胚抗原（CEA）和癌抗原 19-9（CA19-9）进行比较，验证了检测方法的性能。采用 Markov 决策模型进行成本效益分析。
我们开发了一种基于 12 个 miRNA 生物标志物组合的胃癌临床检测方法。在发现和验证队列中，该 12 个 miRNA 组合的曲线下面积（AUC）分别为 0.93（95%CI 0.90 至 0.95）和 0.92（95%CI 0.88 至 0.96）。在前瞻性研究中，特异性为 68.4%（95%CI 67.0%至 69.8%）时，总体敏感性为 87.0%（95%CI 79.4%至 92.5%）。AUC 为 0.848（95%CI 0.81 至 0.88），高于 HP 血清学（0.635）、PG1/2 比值（0.641）、PG 指数（0.576）、ABC 方法（0.647）、CEA（0.576）和 CA19-9（0.595）。每年需要筛查的人数为 489 人。与当前实践相比，该检测方法具有成本效益（增量成本效益比=44531 美元/生命质量年）。
我们开发并验证了一种血清 12 个 miRNA 生物标志物检测方法，它可能是一种用于胃癌风险评估的具有成本效益的方法。
本研究已在 ClinicalTrials.gov 注册（注册号：NCT04329299）。
