Clinical values of detecting global RNA N 6-methyladenosine (m 6A) modification levels and perilipin 2 site-specific m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease
10.3760/cma.j.cn114452-20250107-00019
- VernacularTitle:外周血总RNA m 6A修饰水平和PLIN2特定位点m 6A修饰水平作为冠心病新型分子生物标志物的临床价值
- Author:
Zhuoying GU
1
;
Jia WU
1
;
Xinran WU
1
;
Yanping MO
1
;
Junjun WANG
1
Author Information
1. 江苏大学医学院 东部战区总医院检验科，南京210002
- Publication Type:Journal Article
- Keywords:
Coronary disease;
N 6-methyladenosine modification;
Biomarkers;
Coronary stenosis
- From:
Chinese Journal of Laboratory Medicine
2025;48(7):861-868
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To assess the clinical value of global RNA N6-methyladenosine (m 6A) and perilipin 2 (PLIN2) mRNA site-specific (chr9:19116312) m 6A modification in peripheral blood as novel molecular biomarkers of coronary artery disease (CAD). Methods:Seventy-four patients with coronary artery disease diagnosed at the Eastern Theater General Hospital from June to December 2023, and 60 age-and sex-matched healthy controls during the same period were selected for a retrospective case-control study. The global RNA m 6A modification level in peripheral blood was detected by RNA methylation quantitative detection kit as a preliminary validation, and PLIN2 site-specific (chr9:19116312) m 6A modification level was further detected using the qPCR quantification technique with single-base elongation and ligation as a rescreening validation. Lipid indicators such as total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), routine blood indicators such as neutrophil count and platelet count were detected, and the coronary lesion characteristics were further evaluated by using the Gensini score and SYNTAX score systems in conjunction with coronary arteriography results.The CAD group was divided into a single-branch (25 cases) and a multi-branch lesion subgroup (49 cases) according to the number of vascular lesion branches on coronary angiography. The potential value of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood of patients for the adjunctive diagnosis and assessment of coronary artery disease was explored using Spearman correlation analysis, subject operating characteristic (ROC) curves, and logistic regression analysis. Results:Compared with the control group, the levels of global RNA m 6A modification and PLIN2 site-specific (chr9∶19116312) m 6A modification in peripheral blood were significantly decreased in the CAD group (both P<0.05). The levels of global RNA m 6A modification in peripheral blood was also significantly decreased in the single-branch and multi-branch lesion subgroups ( P<0.05), and PLIN2 site-specific (chr9:19116312) m 6A modification in peripheral blood was significantly decreased in the multi-branch lesion subgroup only ( P<0.05). Spearman correlation analysis showed that in both the CAD group and the multi-branch lesion subgroup, global RNA m 6A modification level in peripheral blood was positively correlated with HDL-C ( r=0.246, 0.289, P<0.05) and negatively correlated with SYNTAX score ( r=-0.261, -0.322, P<0.05) and neutrophil count ( r=-0.246, -0.466, P<0.05). In the single-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with Gensini score ( r=-0.566, P<0.05). In the multi-branch lesion subgroup of CAD, PLIN2 site-specific (chr9:19116312) m 6A modification level was negatively correlated with platelet count ( r=-0.313, P<0.05). The ROC curve analysis showed that the area under the ROC curve (AUC) of global RNA m 6A and PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood for distinguishing CAD and coronary artery multi-branch lesions were 0.915 and 0.918, with specificity of 83.3% and 95.0%, and sensitivity of 85.1% and 75.5%, respectively. The multivariate logistic regression analysis showed that after adjusting confounding factors such as age, sex, proportion of diabetes and hypertension, and TC, the levels of global RNA m 6A modification ( OR=0.691, P<0.001; OR=0.694, P<0.01), and PLIN2 site-specific (chr9:19116312) m 6A modification levels ( OR=0.345, P<0.05; OR=0.143, P<0.01) in peripheral blood remained independently associated with CAD and coronary artery multi-branch lesions, respectively. Conclusions:The analysis of global RNA m 6A in combination with PLIN2 site-specific (chr9:19116312) m 6A modification levels in peripheral blood is valuable for the adjunctive diagnosis and assessment of patients with CAD and coronary artery multi-branch lesions.
