Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Gastric Cancer. 2021 Jul;24(4):835-843. doi: 10.1007/s10120-021-01161-0. Epub 2021 Mar 20.
The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort.
This retrospective case-control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set.
The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953.
A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.
本研究旨在通过大样本队列，确定可区分早期胃癌（EGC）样本与非癌对照的血清 miRNAs。
这是一项回顾性病例对照研究，纳入了 2008 年至 2012 年在日本国家癌症中心医院就诊的 1417 例 EGC 患者（病例组）和 1417 例年龄和性别匹配的非癌对照（对照组）的血清样本。这些样本被随机分配到发现集和验证集中，使用高灵敏度 DNA 芯片（3D-Gene）全面评估全血清样本的 miRNA 表达谱，该芯片设计用于检测 2565 个 miRNA 序列。使用发现集中的几个 miRNA 水平构建诊断模型，并在验证集中评估模型的诊断性能。
发现集由 708 例 EGC 患者和 709 例非癌对照组成，验证集由 709 例 EGC 患者和 708 例非癌对照组成。使用 4 个 miRNAs（miR-4257、miR-6785-5p、miR-187-5p 和 miR-5739）构建了 EGC 诊断指数。在发现集中，EGC 指数的受试者工作特征曲线分析显示，曲线下面积（AUC）为 0.996，灵敏度为 0.983，特异性为 0.977。在验证集中，EGC 指数的 AUC 为 0.998，灵敏度为 0.996，特异性为 0.953。
四种血清 miRNAs 的新组合可能是一种有用的非侵入性诊断生物标志物，可高度准确地检测 EGC。一项多中心前瞻性研究正在进行中，以确认目前的观察结果。
