P16基因甲基化与垂体腺瘤及其临床特征相关性的研究

Research on the relationship between methylation of P16 gene and pituitary adenoma with its clinical features

目的探讨P16基因启动子甲基化在垂体腺瘤形成中的作用,以及P16基因启动子甲基化与垂体腺瘤临床特征之间关系。方法分别提取64例垂体腺瘤患者(垂体瘤组)和32例非垂体瘤患者(对照组)外周静脉血的P16基因,用亚硫酸修饰、PCR扩增、基因克隆及平板克隆测序等技术检测P16基因启动子的甲基化比例。同时对两组患者的P16基因甲基化比例,以及对垂体瘤组中不同肿瘤大小、内分泌功能、复发、瘤卒中、侵袭性、年龄及性别临床特征患者的P16基因的甲基化比例进行比较。结果(1)垂体瘤组甲基化比例明显高于对照组(P<0.05);(2)巨腺瘤组甲基化比例明显高于大腺瘤组和微腺瘤组(均P<0.05),大腺瘤组与微腺瘤组的甲基化比例差异无统计意义(P>0.05);(3)无功能组甲基化比例明显高于激素分泌组(P<0.05);(4)侵袭组甲基化比例明显高于非侵袭组(P<0.05);(5)≥41岁组甲基化比例明显高于30~35岁组和36~40岁组(均P<0.05),30~35岁组与36~40岁组的甲基化比例差异无统计意义(P>0.05);(6)复发组甲基化比例明显高于初发组(P<0.05);(7)伴瘤卒中组与无瘤卒中组的甲基化比例差异无统计意义(P>0.05);(8)男性组与女性组的甲基化比例差异无统计意义(P>0.05)。结论P16基因甲基化与垂体腺瘤的形成、大小、内分泌功能、侵袭性、是否复发以及患者年龄密切相关,而与是否伴有瘤卒中及患者性别无明显关系。

Objective To explore the role of P16 gene promoter methylation in the pituitary adenoma formation,and the relationship between methylation of P16 gene and the clinical features of pituitary adenomas.Methods Patients with pituitary adenoma(clinical pathology confirmed)as the case group,and patients without pituitary adenoma(imaging and endocrinology confirmed)as the control group,P16 gene were extracted from peripheral venous blood of two groups,using the techniques of modified sulfite,PCR amplification,cloning and sequencing to detect the percentage of methylation of P16 gene.By comparing the percentage between two group,and the percentage of size of tumor,endocrine,recurrence,invasion,apoplexy,age and gender in the case group to analyze the relationship between methylation of P16 gene and pituitary adenoma with its clinical features.Results(1)The proportion of methylation in case group was significantly higher than that in control group(P<0.05).(2)The proportion of methylation in giant pituitary adenoma group was significantly higher than that in macroadenoma group and microadenoma group(all P<0.05).There was no significant difference between macroadenoma group and microadenoma group in the proportion of methylation(P>0.05).(3)The proportion of methylation in nonfunction group was significantly higher than that in endocrine group(P<0.05).(4)The proportion of methylation in invasive group was significantly higher than that in non-invasive group(P<0.05).(5)The proportion of methylation in≥41 group was significantly higher than that in 36-40 group and the 30-35 group(all P<0.05).There was no significant difference between the 30-35 group and the 36-40 group in the proportion of methylation(P>0.05).(6)The proportion of methylation in primary adenoma group was significantly higher than that in recurrence group.(P<0.05).(7)There was no significant difference between the tumor apoplexy group and the tumor without apoplexy group in the proportion of methylation(P>0.05).(8)There was no significant difference between male group and female group in the proportion of methylation(P>0.05).Conclusion The methylation of P16 gene is closely related to the formation,size,endocrine,invasiveness,recurrence and age of patients,but not to the apoplexy or gender.