{"title":"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","authors":"Yingli Fu, Jing Jiang, Yanhua Wu, Donghui Cao, Zhifang Jia, Yangyu Zhang, Dongming Li, Yingnan Cui, Yuzheng Zhang, Xueyuan Cao","doi":"10.1007/s10120-024-01493-7","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>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.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>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.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>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, <i>FBXL7, PDE3A, TPO, SNTG2 and STXBP5.</i> 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 (<i>P</i> < 0.001) and GEO external testing data (<i>P</i> < 0.001), and no significant difference between different TNM stage patients (<i>P</i> = 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 (<i>P</i> = 0.10).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>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.</p>","PeriodicalId":12684,"journal":{"name":"Gastric Cancer","volume":"32 1","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer\",\"authors\":\"Yingli Fu, Jing Jiang, Yanhua Wu, Donghui Cao, Zhifang Jia, Yangyu Zhang, Dongming Li, Yingnan Cui, Yuzheng Zhang, Xueyuan Cao\",\"doi\":\"10.1007/s10120-024-01493-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<h3 data-test=\\\"abstract-sub-heading\\\">Background</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Methods</h3><p>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.</p><h3 data-test=\\\"abstract-sub-heading\\\">Results</h3><p>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, <i>FBXL7, PDE3A, TPO, SNTG2 and STXBP5.</i> 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 (<i>P</i> < 0.001) and GEO external testing data (<i>P</i> < 0.001), and no significant difference between different TNM stage patients (<i>P</i> = 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 (<i>P</i> = 0.10).</p><h3 data-test=\\\"abstract-sub-heading\\\">Conclusions</h3><p>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.</p>\",\"PeriodicalId\":12684,\"journal\":{\"name\":\"Gastric Cancer\",\"volume\":\"32 1\",\"pages\":\"\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2024-04-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gastric Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10120-024-01493-7\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gastric Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10120-024-01493-7","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA as noninvasive diagnostic markers for gastric cancer
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.
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.
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