未破裂颅内动脉瘤患者血清微小RNA-504和p53的表达水平及其临床意义

The expression levels and clinical significance of serum microRNA-504 and p53 in patients with unruptured intracranial aneurysms

目的探讨微小RNA-504(miR-504)、p53在未破裂颅内动脉瘤(UIA)患者外周血清中的表达情况及临床意义。方法选取2019年7月至2020年5月于三二〇一医院确诊为UIA患者110例为UIA组,同时选取53例来本院体检的健康人群为对照组。收集患者临床资料,分别检测两组血清中总胆固醇(TC)、甘油三酯(TG)、糖化血红蛋白(HbA1c)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、同型半胱氨酸(Hcy)、N末端B型利钠肽原(NT-proBNP)、肌酐水平;qRT-PCR法检测miR-504表达水平;酶联免疫吸附法检测p53表达水平。Pearson法分析UIA患者血清生化指标与miR-504、p53水平的相关性以及miR-504与p53表达的相关性。使用ROC曲线评估miR-504与p53对UIA的诊断价值。结果与对照组比较,UIA组患者miR-504表达水平明显下调,p53表达水平上调,差异均具有统计学意义(t=17.998、15.995,P<0.05)。血清miR-504水平与CRP、LDL-C、Hcy、NT-proBNP表达均呈正相关(r=0.511、0.295、0.332、0.196,P<0.01),与HDL-C水平呈负相关(r=-0.985,P<0.01);p53与CRP、LDL-C、Hcy、NT-proBNP水平均呈负相关(r=-0.987、-0.583、-0.982、-0.987,P<0.01),与HDL-C水平呈正相关(r=0.992,P<0.01)。UIA患者miR-504和p53的表达水平呈明显负相关(r=-0.345,P<0.05)。ROC结果显示血清miR-504、p53水平诊断UIA的AUC分别为0.984、0.974,对应的敏感度分别为97.27%、92.73%,特异度分别为90.57%、94.34%,两者联合预测UIA的AUC为0.983,敏感度为96.36%,特异度为98.11%。结论miR-504在UIA患者外周血清中明显低表达,p53明显高表达,两者呈明显负相关,并且与CRP、LDL-C、Hcy、NT-proBNP及HDL-C水平具有相关性。两者对UIA都具有诊断价值,可能与UIA的发生和发展密切相关。

Objective To investigate the expression and clinical significance of serum microRNA(miR)-504 and p53 in patients with unruptured intracranial aneurysms(UIA).Methods A total of 110 patients diagnosed as UIA in 3201 Hospital from July 2019 to May 2020 were selected as the UIA group,and 53 healthy people who came to our hospital for physical examination were selected as the control group.The clinical data of patients were collected;the levels of serum total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),and glycosylated hemoglobin(HbA1c),homocysteine(Hcy),N-terminal pro-Btype natriuretic peptide(NT-proBNP)and creatinine in the two groups were detected.The expression level of miR-504 was detected by qRT-PCR.The expression level of p53 was detected by enzymelinked immunosorbent assay(ELISA).The correlation between theserum biochemical indices of UIA patients and the levels of miR-504 and p53 and the correlation between miR-504 and p53 expression were analyzed by Pearson method.ROC curve was used to evaluate the diagnostic value of miR-504and p53 for UIA.Results Compared with the control group,the expression level of miR-504 was significantly down-regulated,and the expression level of p53 was up-regulated,and the differences were statistically significant(t=17.998,15.995;P<0.05).The level of serum mi R-504 was positively correlated with CRP,LDL-C,Hcy and NT-pro BNP(r=0.511,0.295,0.332,0.196;P<0.05),and negatively correlated with the level of HDL-C(r=-0.985,P<0.01);p53 was negatively correlated with the levels of CRP,LDL-C,Hcy and NT-pro BNP(r=-0.987,-0.583,-0.982,-0.987;P<0.05),and positively correlated with the level of HDL-C(r=0.992,P<0.05).The expression levels of mi R-504 and p53 in patients with UIA were significantly negatively correlated(r=-0.345,P<0.05).ROC results showed that AUC of serum mi R-504 and p53 levels predicting UIA were 0.984 and 0.974,corresponding sensitivity was 97.27%and 92.73%respectively,and specificity was 90.575%and 94.34%respectively.The AUC of of combined prediction for UIA was 0.983,the sensitivity was 96.36%,specificity was 98.11%.Conclusion The expression of mi R-504 in the peripheral serum of patients with UIA is significantly low,and the expression of p53 is significantly high.There is a significant negative correlation between the two indicators,and they are significantly correlated with CRP,LDL-C,Hcy,NT-prob NP and HDL-C levels.Mi R-504 and p53 both have diagnostic values for UIA,and may be closely related to the occurrence and development of UIA.