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循环外泌体 hsa_circRNA_0039480 在妊娠期糖尿病中高表达,可作为 GDM 早期诊断的生物标志物。

Circulating exosomal hsa_circRNA_0039480 is highly expressed in gestational diabetes mellitus and may be served as a biomarker for early diagnosis of GDM.

机构信息

Obstetric Clinic The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People's Republic of China.

Jinan Maternity and Child Health Care Hospital, Jinan, Shandong, China.

出版信息

J Transl Med. 2022 Jan 3;20(1):5. doi: 10.1186/s12967-021-03195-5.

DOI:10.1186/s12967-021-03195-5
PMID:34980149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8722188/
Abstract

BACKGROUND

Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM.

METHODS

We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages.

RESULTS

Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P < 0.05). The hsa_circRNA_0039480 expression was higher for GDM group than NGT group at different stages, and was also positively correlated with OGTT during the second trimester (P < 0.05). The expression of hsa_circRNA_0026497 was higher for GDM group during the third, and second trimesters. And there was a strong correlation between two circRNAs in GDM patients during the first-trimester (r = 0.496, P = 0.014). Hsa_circRNA_0039480 showed significant diagnostic value in the first, second, and third trimesters of pregnancy (AUC = 0.704, P = 0.005; AUC = 0.898, P < 0.001 and AUC = 0.698, P = 0.001, respectively). Notably, the combination of hsa_circRNA_0039480 and hsa_circRNA_0026497 exhibited promising discriminative effect on GDM in the first trimesters (AUC = 0.754, P < 0.001).

CONCLUSION

Plasma exosomal hsa_cirRNA_0039480 is highly expressed in GDM patients at different stages and may be served as a candidate biomarker for early detection of GDM.

摘要

背景

妊娠期糖尿病(GDM)严重影响母婴健康,目前尚无有效的早期诊断标志物。因此,有必要寻找用于早期妊娠 GDM 筛查的诊断生物标志物。环状 RNA(circRNA)比线性 RNA 更稳定,可被包裹在外泌体中,并参与各种疾病的病理过程,这使其成为各种疾病更好的候选生物标志物。在本研究中,我们试图鉴定用于检测早期 GDM 的血浆外泌体 circRNA 生物标志物。

方法

我们通过微阵列分析比较了 3 例 GDM 患者分娩前 48 小时和分娩后 48 小时的血浆外泌体 circRNA 表达谱。通过 RT-PCR 分析随机验证 circRNA 表达的重复性。应用 Pearson 相关性分析评估 circRNA 与 OGTT 水平之间的相关性。绘制 ROC 曲线评估 circRNA 在不同阶段对 GDM 的诊断价值。

结果

分娩前 GDM 患者的血浆外泌体 hsa_circRNA_0039480 和 hsa_circRNA_0026497 表达水平较高(P<0.05)。hsa_circRNA_0039480 在不同阶段 GDM 组中的表达高于 NGT 组,并且与孕中期(P<0.05)的 OGTT 呈正相关。hsa_circRNA_0026497 在 GDM 组的孕晚期和孕中期表达水平较高。在孕早期 GDM 患者中,两个 circRNA 之间存在较强的相关性(r=0.496,P=0.014)。hsa_circRNA_0039480 在孕早期、孕中期和孕晚期均具有显著的诊断价值(AUC=0.704,P=0.005;AUC=0.898,P<0.001 和 AUC=0.698,P=0.001)。值得注意的是,hsa_circRNA_0039480 和 hsa_circRNA_0026497 的联合检测在孕早期对 GDM 具有良好的鉴别效果(AUC=0.754,P<0.001)。

结论

血浆外泌体 hsa_cirRNA_0039480 在不同阶段的 GDM 患者中表达水平较高,可能作为 GDM 早期检测的候选生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/63be3ff9f465/12967_2021_3195_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/f6b498659685/12967_2021_3195_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/0aa5334f671f/12967_2021_3195_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/b40768597144/12967_2021_3195_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/920e6f7ec1c6/12967_2021_3195_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/63be3ff9f465/12967_2021_3195_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/f6b498659685/12967_2021_3195_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/0aa5334f671f/12967_2021_3195_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/b40768597144/12967_2021_3195_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/920e6f7ec1c6/12967_2021_3195_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/8722188/63be3ff9f465/12967_2021_3195_Fig5_HTML.jpg

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