Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer

IF 6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gastric Cancer Pub Date : 2024-04-07 DOI:10.1007/s10120-024-01493-7

Yingli Fu, Jing Jiang, Yanhua Wu, Donghui Cao, Zhifang Jia, Yangyu Zhang, Dongming Li, Yingnan Cui, Yuzheng Zhang, Xueyuan Cao

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Abstract

Background

5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection.

Methods

A matched case‒control study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model.

Results

Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10).

Conclusions

The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes’ 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.

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循环细胞游离 DNA 中的全基因组 5-羟甲基胞嘧啶是胃癌的非侵入性诊断标记物

背景5-羟甲基胞嘧啶富集的基因图谱和区域具有组织特异性和肿瘤特异性。方法采用匹配的病例对照研究设计，以50名胃癌患者和50名对照组为研究对象，对细胞游离DNA的不同5-羟甲基胞嘧啶修饰特征进行测序。确定了具有显著差异的 5-羟甲基胞嘧啶修饰基因，从而构建了胃癌诊断模型。结果90%以上的5-羟甲基胞嘧啶峰分布在胃癌组和对照组的基因体内。根据五个不同的5-羟甲基胞嘧啶修饰基因FBXL7、PDE3A、TPO、SNTG2和STXBP5建立了诊断模型。在训练集（AUC = 0.95，灵敏度 = 88.6%，特异度 = 94.3%）、验证集（AUC = 0.87，灵敏度 = 73.3%，特异度 = 93.3%）和测试集（AUC = 0.90，灵敏度 = 81.9%，特异度 = 90.2%）中，该模型能有效区分胃癌患者和对照组。在我们自己的数据（P <0.001）和 GEO 外部检测数据（P <0.001）中，模型中对照组的风险评分明显低于胃癌患者，不同 TNM 分期患者之间也无明显差异（P = 0.09 和 0.66）。结论细胞游离 DNA 中 5- 羟甲基胞嘧啶的特征对胃癌患者具有特异性，由 5 个基因的 5- 羟甲基胞嘧啶特征构建的诊断模型可有效识别胃癌患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gastric Cancer 医学-胃肠肝病学

CiteScore

14.70

自引率

2.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Gastric Cancer is an esteemed global forum that focuses on various aspects of gastric cancer research, treatment, and biology worldwide. The journal promotes a diverse range of content, including original articles, case reports, short communications, and technical notes. It also welcomes Letters to the Editor discussing published articles or sharing viewpoints on gastric cancer topics. Review articles are predominantly sought after by the Editor, ensuring comprehensive coverage of the field. With a dedicated and knowledgeable editorial team, the journal is committed to providing exceptional support and ensuring high levels of author satisfaction. In fact, over 90% of published authors have expressed their intent to publish again in our esteemed journal.