垂体生长激素腺瘤患者血清miR-212与SIRT1表达及与预后相关性

Expressions of miR-212 and SIRT1 in serum of patients with pituitary growth hormone adenoma and their prognostic correlations

目的探讨微小RNA-212(miR-212)、沉默信息调节因子1(SIRT1)在垂体生长激素(GH)腺瘤患者血清中的表达水平及与预后的关系。方法纳入2016年1月~2019年8月空军军医大学第一附属西京医院收诊的58例垂体GH腺瘤患者设为观察组,选取同期于本院体检的62例健康者设为健康组;采用实时荧光定量PCR(qRT-PCR)法检测所有研究对象血清miR-212、SIRT1、缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)表达水平;比较不同预后垂体GH腺瘤患者血清miR-212、SIRT1、HIF-1α、VEGF水平;采用Pearson法分析垂体GH腺瘤患者血清miR-212、SIRT1表达水平与HIF-1α、VEGF相关性及miR-212表达水平与SIRT1的关系;采用受试者特征工作曲线(ROC)评价血清miR-212、SIRT1对垂体GH腺瘤患者预后的诊断价值。结果观察组患者血清miR-212表达水平明显低于健康组(t=7.434,P<0.05),血清SIRT1、HIF-1α、VEGF表达水平明显高于健康组(P<0.05);未缓解组垂体GH腺瘤患者血清miR-212表达水平明显低于缓解组(P<0.05),血清SIRT1、HIF-1α、VEGF表达水平明显高于缓解组(t=2.536、3.242、2.638,P<0.05);垂体GH腺瘤患者血清miR-212表达水平与HIF-1α、VEGF、SIRT1水平均呈负相关(P<0.05),血清SIRT1表达水平与HIF-1α、VEGF呈正相关(P<0.05);血清miR-212、SIRT1水平对垂体GH腺瘤患者不良预后评估的曲线下面积(AUC)为0.873、0.862,对应截断值分别为0.52、1.94,此时对应灵敏度分别为81.3%、75.0%,特异度分别为88.1%、85.7%;两者联合诊断垂体GH腺瘤的AUC为0.938,其灵敏度、特异度分别为93.8%、81.0%。结论垂体GH腺瘤血清miR-212表达下调,SIRT1表达上调,两者可能与HIF-1α、VEGF相互作用,进而协同垂体GH腺瘤发生与发展,miR-212、SIRT1有望成为评估垂体GH腺瘤预后的参考指标,两者联合检测可有效提高垂体GH腺瘤预后价值。

Objective To investigate the expression levels of microRNA-212(miR-212)and silent information regulator 1(SIRT1)in the serum of patients with pituitary growth hormone(GH)adenoma and their relationships with prognosis.Methods 58 patients with GH adenoma admitted to our hospital from January 2016 to August 2019 were selected for the study,and 62 healthy people who were examined in our hospital at the same time were selected for the control study.The expression levels of miR-212,SIRT1,hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by real-time fluorescent quantitative PCR(qRT-PCR).The levels of serum miR-212,SIRT1,HIF-1αand VEGF in GH adenomas with different prognosis were compared.Pearson's method was used to analyze the correlations between the expression levels of miR-212,SIRT1 and HIF-1α,VEGF,and the relationship between the expressions of miR-212 and SIRT1.The diagnostic values of serum miR-212 and SIRT1 in the prognosis of GH adenoma patients were evaluated by receiver operating characteristic curve(ROC).Results The expression level of miR-212 in the patients with GH adenoma was significantly lower than that in the healthy group(t=7.434,P<0.05),while the levels of SIRT1,HIF-1αand VEGF in serum were significantly higher than those in healthy group(P<0.05).The expression level of miR-212 in the non remission group was significantly lower than that in the remission group(P<0.05),while the expression levels of SIRT1,HIF-1αand VEGF in serum were significantly higher than those in the remission group(t=2.536,3.242,2.638,P<0.05).The expression level of miR-212 was negatively correlated with the levels of HIF-1α,VEGF and SIRT1 in GH adenoma patients(P<0.05),and the expression level of SIRT1 was positively correlated with HIF-1αand VEGF(P<0.05).The areas under the curve(AUCs)of serum miR-212 and SIRT1 levels in the evaluation of poor prognosis of GH adenoma patients were 0.873 and 0.862,and the corresponding cutoff values were 0.52 and 1.94,respectively.The corresponding sensitivities were 81.3%and 75.0%,and the specificities were 88.1%and 85.7%,respectively.The AUC of the combination in the evaluation of GH adenoma was 0.938,and the sensitivity and specificity were 93.8%and 81.0%,respectively.Conclusion The expression of miR-212 in serum of GH pituitary adenoma is down-regulated,and the expression of SIRT1 is up-regulated.They may interact with HIF-1αand VEGF,and then cooperate with the occurrence and development of GH adenoma.miR-212 and SIRT1 are expected to be the reference indexes to evaluate the prognosis of GH pituitary adenomas.The combination of them can effectively improve the prognosis value of GH pituitary adenomas.