目的 甲状腺癌(TC)患者血清微小RNA-302e(miR-302e),MYC结合蛋白2(MYCBP2)及共刺激分子(B7-H3)表达水平与临床分期和预后的相关性研究.方法 选取本院2018年7月至2020年7月期间接诊的138例TC患者作为疾病组,同期选取138例进行体检的健康者作为对照组.根据对患者随访3年的结果,将疾病组分为预后不良组(n=20)和预后良好组(n=118).采用qRT-PCR法检测血清miR-302e、MYCBP2水平,ELISA法检测血清B7-H3水平;TargetScanHuman网站预测miR-302e与MYCBP2的靶向关系;运用ROC曲线分析血清miR-302e,MYCBP2,B7-H3对TC患者预后的预测价值.结果 与对照组(1.05±0.23、1.03±0.22、28.46±4.18μg/L)相比,疾病组血清 miR-302e(1.78±0.40),B7-H3(34.33±5.94μg/L)水平明显升高,血清MYCBP2(0.82±0.15)水平降低,差异有统计学意义(t=18.586,9.265,9.494,P＜0.05);与临床分期Ⅰ+Ⅱ期患者(1.65±0.37、0.90±0.15、32.68±3.29μg/L)相比,Ⅲ+Ⅳ 期患者血清 miR-302e(2.16±0.48),B7-H3(39.20±4.08μg/L)水平明显升高,血清MYCBP2(0.58±0.14)水平降低,差异有统计学意义(t=6.511,9.510,11.084,P＜0.05);预后不良组临床分期Ⅲ期+Ⅳ期占比、淋巴结转移占比、血清miR-302e(2.16±0.45),B7-H3水平(43.26±6.85μg/L)显著高于预后良好组,血清 MYCBP2(0.58±0.11)低于预后良好组(1.72±0.39、0.86±0.16、32.82±5.79μg/L),差异有统计学意义(x2=10.954,24.620,t=4.561,7.519,7.257,P＜0.05);MYCBP2 与 miR-302e 可能有靶向关系,且经 Pearson 相关性分析,MYCBP2 与 miR-302e呈负相关性(r=-0.513,P＜0.001);血清miR-302e,MYCBP2,B7-H3、临床分期、淋巴结转移是TC患者预后的影响因素(P＜0.05);血清miR-302e,MYCBP2,B7-H3联合预测TC患者预后的曲线下面积(AUC)为0.975,优于各自单独预测(Z联合 vs miR-302e=2.448、Z联合 vs MYCBP2=3.024、Z联合 vs B7-H3=2.133,P=0.014、0.003、0.033).结论 TC 患者血清 miR-302e,B7-H3水平明显升高,血清MYCBP2明显降低,与患者临床分期及预后密切相关,3项联合检测对患者预后有更高的预测价值.
The Correlation Between Serum MiR-302e,MYCBP2,and B7-H3 Expression Levels and Clinical Staging and Prognosis in Patients with Thyroid Cancer
Objective To investigate the correlation between expression levels of serum microRNA-302e(miR-302e),MYC binding protein 2(MYCBP2),and co-stimulatory molecules(B7-H3)in patients with thyroid cancer(TC)and clinical staging and prognosis.Methods A total of 138 TC patients admitted to our hospital from July,2018 to July,2020 were collected as the disease group,while 138 healthy individuals who underwent physical examinations during the same period were regarded as the control group.Based on the results of a 3-year follow-up of patients,the disease group was further separated into a poor prognosis group(n=20)and a good prognosis group(n=118).QRT-PCR method was applied to detect serum miR-302e and MYCBP2 levels,and ELISA method was applied to detect serum B7-H3 level;TargetScanHuman website was utilized to predict the targeting relationship between miR-302e and MYCBP2;ROC curve was drawn to evaluate predictive values of serum miR-302e,MYCBP2,and B7-H3 for the prognosis of TC patients.Results Compared with the control group(1.05±0.23,1.03±0.22,28.46±4.18μg/L),serum levels of miR-302e(1.78±0.40)and B7-H3(34.33±5.94μg/L)in the disease group were significantly increased,while serum level of MYCBP2(0.82±0.15)was reduced,and the difference was statistically significant(t=18.586,9.265,9.494,P＜0.05);Compared with clinical stage Ⅰ+Ⅱ patients(1.65±0.37,32.68±3.29μg/L,0.90±0.15),serum miR-302e(2.16±0.48)and B7-H3(39.20±4.08µg/L)levels were significantly increased in stage Ⅲ+Ⅳ patients,while serum MYCBP2(0.58±0.14)level was reduced,and he difference was statistically significant(t=6.511,9.510,11.084,P＜0.05);The proportions of stage Ⅲ+Ⅳ,lymph node metastasis,the levels of serum miR-302e(2.16±0.45),and B7-H3(43.26±6.85μg/L)in the poor prognosis group were significantly higher than those in the good prognosis group,while serum MYCBP2(0.58±0.11)was lower than that in the good prognosis group,(1.72±0.39,0.86±0.16,32.82±5.79μg/L),and the difference was statistically significant(X2=10.954,24.620,t=4.561,7.519,7.257,P＜0.05);MYCBP2 showed a targeting relationship with miR-302e,and Pearson correlation analysis identified a negative correlation between MYCBP2 and miR-302e(r=-0.513,P＜0.001);Serum miR-302e,MYCBP2,B7-H3,clinical stage and lymph node metastasis were the prognostic factors of TC patients(P＜0.05).The area under the curve(AUC)of the combination of serum miR-302e,MYCBP2,and B7-H3 for predicting the prognosis of TC patients was 0.975,which was better than those individual predictions(Zcombination vs miR-302e=2.448,Zcombination vs MYCBP2=3.024,Zcombination vs B7-H3=2.133,P=0.014,0.003,0.033).Conclusion Serum levels of miR-302e and B7-H3 in TC patients are significantly elevated,while serum MYCBP2 is significantly reduced,which is closely related to the clinical stage and prognosis of patients.The combined detection of these three markers has a higher predictive value for prognosis.
Thyroid cancerMicro RNA-302eMYC binding protein 2Co stimulatory moleculesClinical stagingPrognosis
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