A novel combination of serum microRNAs for the detection of early gastric cancer,Gastric Cancer

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A novel combination of serum microRNAs for the detection of early gastric cancer
Gastric Cancer ( IF 6.0 ) Pub Date : 2021-03-20 , DOI: 10.1007/s10120-021-01161-0
Seiichiro Abe ₁ , Juntaro Matsuzaki ₂ , Kazuki Sudo ₃ , Ichiro Oda ₁ , Hitoshi Katai ₄ , Ken Kato ₅ , Satoko Takizawa _{2,

6} , Hiromi Sakamoto ₇ , Fumitaka Takeshita ₈ , Shumpei Niida ₉ , Yutaka Saito ₁ , Takahiro Ochiya _{2,

10}

Affiliation

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan.
Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan.
Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Toray Industries, Inc., Kanagawa, Japan.
Department of Biobank and Tissue Resources, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan.
Department of Translational Oncology, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan.
National Center for Geriatrics and Gerontology, Research Institute, Aichi, Japan.
Department of Molecular and Cellular Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

中文翻译：

一种用于检测早期胃癌的血清 microRNA 新组合

背景

本研究的目的是使用大型队列鉴定血清 miRNA，这些 miRNA 可将早期胃癌 (EGC) 样本与非癌症对照样本区分开来。

方法

这项回顾性病例对照研究包括来自 EGC 患者（2008 年至 2012 年在东京国立癌症中心医院）和 1417 名年龄和性别匹配的非癌症对照者的 1417 份血清样本。样本被随机分配到发现和验证集，并使用专为检测 2565 个 miRNA 序列而设计的高灵敏度 DNA 芯片 (3D-Gene ^® )全面评估全血清样本的 miRNA 表达谱。使用发现集中几种miRNA的水平构建诊断模型，并在验证集中评估模型的诊断性能。

结果

发现集由来自 EGC 患者的 708 个样本和来自非癌症对照的 709 个样本组成，验证集由来自 EGC 患者的 709 个样本和来自非癌症对照的 708 个样本组成。使用四种 miRNA（miR-4257、miR-6785-5p、miR-187-5p 和 miR-5739）构建诊断 EGC 指数。在发现集中，EGC指数的接受者操作特征曲线分析显示曲线下面积（AUC）为0.996，敏感性为0.983，特异性为0.977。在验证集中，EGC 指数的 AUC 为 0.998，敏感性为 0.996，特异性为 0.953。