Jin Wang, Pengyu Huang, Fei Hou, Dongdong Hao, Wushan Li, Hua Jin
{"title":"预测妊娠 11-13 周时的妊娠糖尿病风险：染色体外环状 DNA 的作用。","authors":"Jin Wang, Pengyu Huang, Fei Hou, Dongdong Hao, Wushan Li, Hua Jin","doi":"10.1186/s12933-024-02381-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) significantly impacts maternal and infant health both immediately and over the long term, yet effective early diagnostic biomarkers are currently lacking. Thus, it is essential to identify early diagnostic biomarkers for GDM risk screening. Extrachromosomal circular DNA (eccDNA), being more stable than linear DNA and involved in disease pathologies, is a viable biomarker candidate for diverse conditions. In this study, eccDNA biomarkers identified for early diagnosis and assessment of GDM risk were explored.</p><p><strong>Methods: </strong>Using Circle-seq, we identified plasma eccDNA profiles in five pregnant women who later developed GDM and five matched healthy controls at 11-13 weeks of gestation. These profiles were subsequently analyzed through bioinformatics and validated through outward PCR combined with Sanger sequencing. Furthermore, candidate eccDNA was validated by quantitative PCR (qPCR) in a larger cohort of 70 women who developed GDM and 70 normal glucose-tolerant (NGT) subjects. A ROC curve assessed the eccDNA's diagnostic potential for GDM.</p><p><strong>Results: </strong>2217 eccDNAs were differentially detected between future GDM patients and controls, with 1289 increased and 928 decreased in abundance. KEGG analysis linked eccDNA genes mainly to GDM-related pathways such as Rap1, MAPK, and PI3K-Akt, and Insulin resistance, among others. Validation confirmed a significant decrease in eccDNA PRDM16<sup>circle</sup> in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16<sup>circle</sup> showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001).</p><p><strong>Conclusions: </strong>Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16<sup>circle</sup>, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker.</p><p><strong>Trial registration: </strong>ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":null,"pages":null},"PeriodicalIF":8.5000,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304788/pdf/","citationCount":"0","resultStr":"{\"title\":\"Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.\",\"authors\":\"Jin Wang, Pengyu Huang, Fei Hou, Dongdong Hao, Wushan Li, Hua Jin\",\"doi\":\"10.1186/s12933-024-02381-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) significantly impacts maternal and infant health both immediately and over the long term, yet effective early diagnostic biomarkers are currently lacking. Thus, it is essential to identify early diagnostic biomarkers for GDM risk screening. Extrachromosomal circular DNA (eccDNA), being more stable than linear DNA and involved in disease pathologies, is a viable biomarker candidate for diverse conditions. In this study, eccDNA biomarkers identified for early diagnosis and assessment of GDM risk were explored.</p><p><strong>Methods: </strong>Using Circle-seq, we identified plasma eccDNA profiles in five pregnant women who later developed GDM and five matched healthy controls at 11-13 weeks of gestation. These profiles were subsequently analyzed through bioinformatics and validated through outward PCR combined with Sanger sequencing. Furthermore, candidate eccDNA was validated by quantitative PCR (qPCR) in a larger cohort of 70 women who developed GDM and 70 normal glucose-tolerant (NGT) subjects. A ROC curve assessed the eccDNA's diagnostic potential for GDM.</p><p><strong>Results: </strong>2217 eccDNAs were differentially detected between future GDM patients and controls, with 1289 increased and 928 decreased in abundance. KEGG analysis linked eccDNA genes mainly to GDM-related pathways such as Rap1, MAPK, and PI3K-Akt, and Insulin resistance, among others. Validation confirmed a significant decrease in eccDNA PRDM16<sup>circle</sup> in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16<sup>circle</sup> showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001).</p><p><strong>Conclusions: </strong>Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16<sup>circle</sup>, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker.</p><p><strong>Trial registration: </strong>ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.</p>\",\"PeriodicalId\":9374,\"journal\":{\"name\":\"Cardiovascular Diabetology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.5000,\"publicationDate\":\"2024-08-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11304788/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular Diabetology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12933-024-02381-1\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Diabetology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12933-024-02381-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Predicting gestational diabetes mellitus risk at 11-13 weeks' gestation: the role of extrachromosomal circular DNA.
Background: Gestational diabetes mellitus (GDM) significantly impacts maternal and infant health both immediately and over the long term, yet effective early diagnostic biomarkers are currently lacking. Thus, it is essential to identify early diagnostic biomarkers for GDM risk screening. Extrachromosomal circular DNA (eccDNA), being more stable than linear DNA and involved in disease pathologies, is a viable biomarker candidate for diverse conditions. In this study, eccDNA biomarkers identified for early diagnosis and assessment of GDM risk were explored.
Methods: Using Circle-seq, we identified plasma eccDNA profiles in five pregnant women who later developed GDM and five matched healthy controls at 11-13 weeks of gestation. These profiles were subsequently analyzed through bioinformatics and validated through outward PCR combined with Sanger sequencing. Furthermore, candidate eccDNA was validated by quantitative PCR (qPCR) in a larger cohort of 70 women who developed GDM and 70 normal glucose-tolerant (NGT) subjects. A ROC curve assessed the eccDNA's diagnostic potential for GDM.
Results: 2217 eccDNAs were differentially detected between future GDM patients and controls, with 1289 increased and 928 decreased in abundance. KEGG analysis linked eccDNA genes mainly to GDM-related pathways such as Rap1, MAPK, and PI3K-Akt, and Insulin resistance, among others. Validation confirmed a significant decrease in eccDNA PRDM16circle in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16circle showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001).
Conclusions: Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16circle, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker.
Trial registration: ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.
期刊介绍：
Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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