Diabetes Research Center, Medical School, Ningbo University, 818 Fenghua Road, Ningbo, 315211, Zhejiang, China.
Department of Gynaecology and Obstetrics, Ningbo University Medical Center Lihuili Eastern Hospital, Taipei Medical University, 1111 Jiangnan Road, Ningbo, 315048, Zhejiang, China.
Clin Epigenetics. 2019 Feb 8;11(1):22. doi: 10.1186/s13148-019-0610-8.
Circular RNA (circRNA) is involved in the pathological processes of various diseases. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM).
A retrospective case-control study was conducted using data and samples from women treated at a hospital in China between July 10, 2017, and February 15, 2018. We collected serum samples from 40 healthy pregnant women (controls) and 40 women with GDM (cases) during the second trimester as well as 65 controls and 65 cases during the third trimester of pregnancy. Placenta tissues and neonatal cord blood were each from another 20 cases and 20 controls. We selected six circRNAs (hsa_circRNA_0054633, hsa_circRNA_103410, hsa_circRNA_063981, hsa_circRNA_102682, hsa_circRNA_0018508, and hsa_circRNA_406918) as candidate biomarkers and used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to measure their concentrations in the serum and placental tissues. The Pearson correlation test was used to assess the correlation between various circRNAs and between circRNA and clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs for GDM at each stage.
Hsa_circRNA_0054633 was highly expressed in the blood during the second and third trimesters; its expression was also high in the placenta but low in the cord blood (P < 0.05). Hsa_cirRNA_0054633 was highly correlated with GHBA1 and GHBA1c levels in maternal blood samples at various stages of the GDM group (including placental tissue and umbilical cord blood) (P < 0.05). Hsa_circRNA_063981, hsa_circRNA_102682, and hsa_circRNA_103410 were also differentially expressed between the case and control groups at different stages (P < 0.05). There was a strong correlation between hsa_circRNA_0054633 and hsa_circRNA_103410 levels in third-trimester maternal blood (P = 0.000, r = 0.554) and in neonatal umbilical cord blood (P = 0.000, r = 0.866). Hsa_circRNA_0054633 showed a significant diagnostic value in the second and third trimesters of pregnancy, placenta, and cord blood (AUC = 0.793, 0.664, 0.747, and 0.783, respectively, P < 0.001).
This study suggests that hsa_cirRNA_0054633 is abnormally expressed in GDM patients and may play a potential role in the development of GDM. The possibility of using circRNAs for the diagnosis of GDM requires additional investigation in future studies.
环状 RNA（circRNA）参与各种疾病的病理过程。circRNA 比线性 RNA 更稳定，在组织中表达水平较高，因此比线性 RNA 更适合作为生物标志物候选物。本研究旨在鉴定妊娠期糖尿病（GDM）的潜在 circRNA 生物标志物。
采用回顾性病例对照研究，收集 2017 年 7 月 10 日至 2018 年 2 月 15 日期间在中国一家医院治疗的妇女的数据和样本。我们收集了 40 名健康孕妇（对照组）和 40 名 GDM 妇女（病例组）在妊娠中期以及 65 名对照组和 65 名病例组在妊娠晚期的血清样本。胎盘组织和新生儿脐血各来自另外 20 例病例和 20 例对照。我们选择了 6 个 circRNA（hsa_circRNA_0054633、hsa_circRNA_103410、hsa_circRNA_063981、hsa_circRNA_102682、hsa_circRNA_0018508 和 hsa_circRNA_406918）作为候选生物标志物，并使用定量逆转录聚合酶链反应（qRT-PCR）测量它们在血清和胎盘组织中的浓度。Pearson 相关检验用于评估各种 circRNA 之间以及 circRNA 与临床变量之间的相关性。接受者操作特征（ROC）曲线下面积用于评估 circRNA 在每个阶段对 GDM 的诊断价值。
hsa_circRNA_0054633 在妊娠中期和晚期的血液中表达水平较高；在胎盘组织中也有较高的表达，但在脐血中表达水平较低（P<0.05）。hsa_circRNA_0054633 与 GDM 组（包括胎盘组织和脐血）各阶段母体血液中的 GHBA1 和 GHBA1c 水平高度相关（P<0.05）。hsa_circRNA_063981、hsa_circRNA_102682 和 hsa_circRNA_103410 在不同阶段的病例组和对照组之间也存在差异表达（P<0.05）。在妊娠晚期母亲的血液（P=0.000，r=0.554）和新生儿脐血（P=0.000，r=0.866）中，hsa_circRNA_0054633 水平与 hsa_circRNA_103410 水平之间存在很强的相关性。hsa_circRNA_0054633 在妊娠中期和晚期、胎盘和脐血中具有显著的诊断价值（AUC=0.793、0.664、0.747 和 0.783，P<0.001）。
本研究表明 hsa_circRNA_0054633 在 GDM 患者中异常表达，可能在 GDM 的发展中发挥潜在作用。使用 circRNAs 进行 GDM 诊断的可能性需要在未来的研究中进一步研究。
