Wang Jin, Huang Pengyu, Hou Fei, Hao Dongdong, Li Wushan, Jin Hua
Prenatal Diagnosis Center, Jinan Maternal and Child Health Care Hospital, No.2, Jianguo Xiaojing Roud, Jinan, 250002, Shandong Province, People's Republic of China.
Fujian Provincial Sperm Bank, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350005, Fujian Province, People's Republic of China.
Cardiovasc Diabetol. 2024 Aug 7;23(1):289. doi: 10.1186/s12933-024-02381-1.
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.
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.
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 in the plasma of 70 women who developed GDM compared to 70 NGT women, consistent with the eccDNA-seq results. PRDM16 showed significant diagnostic value in 11-13 weeks of gestation (AUC = 0.941, p < 0.001).
Our study first demonstrats that eccDNAs are aberrantly produced in women who develop GDM, including PRDM16, which can predict GDM at an early stage of pregnancy, indicating its potential as a biomarker.
ChiCTR2300075971, http://www.chictr.org.cn . Registered 20 September 2023.
妊娠期糖尿病（GDM）对母婴健康有着即时和长期的重大影响，但目前缺乏有效的早期诊断生物标志物。因此，识别用于GDM风险筛查的早期诊断生物标志物至关重要。染色体外环状DNA（eccDNA）比线性DNA更稳定，且参与疾病病理过程，是多种疾病中一种可行的生物标志物候选物。在本研究中，探索了用于早期诊断和评估GDM风险的eccDNA生物标志物。
使用Circle-seq技术，我们在5名后来发展为GDM的孕妇和5名匹配的健康对照妊娠11-13周时鉴定了血浆eccDNA图谱。随后通过生物信息学分析这些图谱，并通过外切PCR结合桑格测序进行验证。此外，在70名发展为GDM的女性和70名糖耐量正常（NGT）受试者的更大队列中，通过定量PCR（qPCR）验证候选eccDNA。ROC曲线评估了eccDNA对GDM的诊断潜力。
在未来的GDM患者和对照组之间差异检测到2217个eccDNA，其中丰度增加的有1289个，减少的有928个。KEGG分析将eccDNA基因主要与GDM相关途径如Rap1、MAPK和PI3K-Akt以及胰岛素抵抗等联系起来。验证证实，与70名NGT女性相比，70名发展为GDM的女性血浆中eccDNA PRDM16显著降低，与eccDNA-seq结果一致。PRDM16在妊娠11-13周时显示出显著的诊断价值（AUC = 0.941，p < 0.001）。
我们的研究首次证明，在发展为GDM的女性中eccDNA异常产生，包括PRDM16，其可在妊娠早期预测GDM，表明其作为生物标志物的潜力。
ChiCTR2300075971，http://www.chictr.org.cn 。于2023年9月20日注册。
