Efficacy analysis of a preeclampsia risk prediction model based on exosomal multiple miRNA expression levels

doi:10.11958/20230485

Abstract

Abstract:

Objective To investigate the feasibility of constructing a preeclampsia (PE) risk model based on multiple exosomal micrornas (miRNA) expression levels and to verify its efficacy in predicting PE. Methods A total of 1 037 pregnant women who were archived in our hospital from June 2019 to December 2021 and whose gestational weeks were less than or equal to 20 weeks were selected as the research subjects. The expression of exosomal miRNA (including miR-155-5p, miR-215-5p, miR-203a-3p, miR-199a-5p and miR-125a-3p) in all samples was detected by qRT-PCR. Then, all patients were followed up to the end of pregnancy. The occurrence of PE during the follow-up period was counted, and all samples were divided into the PE group and the control group according to results. Cox regression was used to analyze the influencing factors of PE. The multi-miRNA risk model was constructed with ggrisk package, and the predictive effect of the model on PE was evaluated by receiver operating characteristic (ROC) curve. Results By the end of follow-up on October 31, 2022, 974 cases were finally followed up, and the follow-up completion rate was 93.92%. Among all the 974 patients who completed the follow-up, 65 patients developed PE, so they were finally divided into the PE group, and 909 cases were used as the control group. The age, pre-pregnancy BMI and waist circumference at 12 weeks of gestation were higher in the PE group than those in the control group (P<0.05). The proportions of smoking history and drinking history were higher in the PE group than those of the control group (P<0.05). The contents of triglyceride (TG), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), alanyl aminotransferase (ALT), aspartate aminotransferase (AST), platelet distribution width (PDW), mean platelet volume (MPV), miR-155-5p, miR-199a-5p and miR-215-5p were higher in the PE group than those in the control group，while contents of thyroid stimulating hormone (TSH), miR-125a-3p and miR-203a-3p were lower in the PE group than those in the control group (P<0.05). The expression levels of miR-125a-3p, miR-155-5p, miR-199a-5p and miR-215-5p were independent predictors of PE (P<0.05). The predictive risk model constructed from the above miRNAs had good predictive value in the occurrence of PE (AUC=0.998), with a sensitivity of 98.46% (63/65) and a specificity of 93.94% (854/909). Conclusion miR-125a-3p, miR-155-5p, miR-199a-5p, miR-203a-3p and miR-215-5p are significantly related to the occurrence of PE, and the PE prediction model constructed with the above five miRNAs has better effect.

Key words: pre-eclampsia, exosomes, microRNAs, predict model

CLC Number:

R714.252

Figures/Tables 7

References 24

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基因名称	引物序列（5′→3′）	产物大小/bp
miR-125a- 3p	上游：ACGTGTGTAGCTTATCAGACTG	22
miR-125a- 3p	下游：AATGGTTGTTCTCCACACTCTC	22
miR-155- 5p	上游：GAGGGTTAATGCTAATCGTGATAGG	25
miR-155- 5p	下游：GCACAGAATCAACACGACTCACTAT	25
miR-199a- 5p	上游：TTATTACCCAGGCAGACACCG	21
miR-199a- 5p	下游：AGTGCGAACTGTGGCGATGC	21
miR-203a- 3p	上游：CCGGTGAAATGTTTAGGACC	20
miR-203a- 3p	下游：GCCGCGTGAAAATGTTTAGG	20
miR-215- 5p	上游：CTCGAGATGTCATCCTCAG	19
miR-215- 5p	下游：GAATTCGTGAGTTCTTCTG	19
U6	上游：CTTCGGCAGCACATATAC	18
U6	下游：GAACGCTTCACGAATTTG	18

基因名称	引物序列（5′→3′）	产物大小/bp
miR-125a- 3p	上游：ACGTGTGTAGCTTATCAGACTG	22
miR-125a- 3p	下游：AATGGTTGTTCTCCACACTCTC	22
miR-155- 5p	上游：GAGGGTTAATGCTAATCGTGATAGG	25
miR-155- 5p	下游：GCACAGAATCAACACGACTCACTAT	25
miR-199a- 5p	上游：TTATTACCCAGGCAGACACCG	21
miR-199a- 5p	下游：AGTGCGAACTGTGGCGATGC	21
miR-203a- 3p	上游：CCGGTGAAATGTTTAGGACC	20
miR-203a- 3p	下游：GCCGCGTGAAAATGTTTAGG	20
miR-215- 5p	上游：CTCGAGATGTCATCCTCAG	19
miR-215- 5p	下游：GAATTCGTGAGTTCTTCTG	19
U6	上游：CTTCGGCAGCACATATAC	18
U6	下游：GAACGCTTCACGAATTTG	18

组别	n	年龄/岁	孕前BMI/ （kg/m²）	孕12周腰围/cm	饮酒史	吸烟史	高血压	收缩压/mmHg	舒张压/mmHg	孕≥2次
对照组	909	27.28±3.89	21.53±1.62	77.54±3.83	67（7.4）	90（9.9）	114（12.5）	115.66±6.68	77.51±5.42	288（31.7）
PE组	65	29.85±6.46	21.99±3.07	80.97±8.67	10（15.4）	14（21.5）	9（13.8）	115.31±8.33	76.89±4.34	26（40.0）
t或χ²		4.895^＊＊	2.027^＊	6.189^＊＊	5.351^＊	8.631^＊＊	0.093	0.408	0.902	1.921

组别	n	年龄/岁	孕前BMI/ （kg/m²）	孕12周腰围/cm	饮酒史	吸烟史	高血压	收缩压/mmHg	舒张压/mmHg	孕≥2次
对照组	909	27.28±3.89	21.53±1.62	77.54±3.83	67（7.4）	90（9.9）	114（12.5）	115.66±6.68	77.51±5.42	288（31.7）
PE组	65	29.85±6.46	21.99±3.07	80.97±8.67	10（15.4）	14（21.5）	9（13.8）	115.31±8.33	76.89±4.34	26（40.0）
t或χ²		4.895^＊＊	2.027^＊	6.189^＊＊	5.351^＊	8.631^＊＊	0.093	0.408	0.902	1.921

组别		n	FPG/（mmol/L）		TG/（mmol/L）		LDL-C/（mmol/L）			TC/（mmol/L）		ALT/（U/L）		AST/（U/L）
对照组		909	5.11±1.41		1.89±0.47		3.08±0.60			5.64±0.89		23.24±5.42		18.41±4.11
PE组		65	5.22±1.98		2.05±0.72		3.31±1.15			5.91±1.89		25.16±8.42		19.75±4.31
t			0.584		2.558^＊		2.756^＊＊			2.111^＊		2.643^＊＊		2.524^＊
组别	PLT/（×10⁹/L）			Hb/（g/L）		PDW/%		MPV/fL	TSH/（U/L）		FT3/（pmol/L）		FT4/（pmol/L）
对照组	214.59±37.01			123.43±9.33		15.30±2.04		8.77±2.01	2.25±0.39		4.25±0.42		12.56±1.91
PE组	219.36±57.39			126.47±10.35		17.60±4.27		9.98±2.96	1.95±0.34		4.29±0.64		12.95±3.21
t	0.961			2.519^＊		7.933^＊＊		4.516^＊＊	6.070^＊＊		0.664		1.529