DLC-1启动子甲基化与垂体腺瘤侵袭性的关系

目的：研究肝癌缺失基因1(DLC-1)启动子区CpG甲基化与人垂体腺瘤侵袭性的关系，探讨垂体腺瘤发生发展的分子机制。方法收集84例垂体腺瘤标本和6例尸检时获得的正常人垂体组织标本，利用实时荧光定量PCR的方法检测标本中DLC-1的表达水平，利用特异性聚合酶链反应(MSP)检测DLC-1基因启动子区CpG甲基化状态。结果 DLC-1在垂体腺瘤标本中表达下降。6例正常人垂体组织标本中DLC-1基因启动子区无甲基化，49例侵袭性垂体腺瘤标本中有19例发生甲基化(38.78%)，35例非侵袭性垂体腺瘤标本中有3例发生甲基化(8.57%)，52例功能性垂体腺瘤标本中有15例发生甲基化（28.84%），32例无功能性垂体腺瘤标本中有7例发生甲基化(21.88%)。DLC-1在侵袭性垂体腺瘤组与非侵袭性垂体腺瘤组之间发生甲基化率比较差异有统计学意义（P<0.05)，而在功能性垂体腺瘤组与无功能性垂体腺瘤组之间发生甲基化率比较差异无统计学意义(P>0.05)。DLC-1启动子甲基化与垂体腺瘤DLC-1表达量呈负相关(r=-0.67，P=0.01)。结论 DLC-1基因启动子甲基化跟垂体腺瘤的发生发展有关，可作为垂体腺瘤侵袭性发生的重要标志。

Relationship between DLC-1 promoter methylation and invasion of pituitary adenomas

Objective To study the relationship between CpG methylation in promoter region of deleted in liv-er cancer-1 (DLC-1) and invasion of human pituitary adenomas, and to explore the molecular mechanisms of the occur-rence and development of the pituitary adenoma. Methods Pituitary tissue samples were collected from patients with pituitary adenomas (n=84) and normal people (n=6, by autopsy). Real-time quantitative PCR was used to detect DLC-1 expression levels, and methylation-specific polymerase chain reaction (MSP) was used to detect the CpG methylation status in promoter region of DLC-1 gene. Results DLC-1 expression decreased in samples of pituitary adenomas. The 6 cases of normal human pituitary tissue samples showed no methylation in DLC-1 gene promoter region. Methylation was found in 19 cases (38.78%) among the 49 cases of invasive pituitary adenoma specimens, 3 cases (8.57%) among 35 cases of noninvasive pituitary adenomas, 15 cases (28.84%) among the 52 cases of functional pituitary adenomas, and 7 cases (21.88%) among 32 cases of non-functional pituitary adenomas. There was a significant difference in the incidence of methylation between the invasive pituitary adenomas group and noninvasive pituitary adenomas group (P<0.05). There was no significant difference in the incidence of methylation between the functional pituitary adenoma group and the non-functional pituitary adenoma group (P>0.05). DLC-1 gene promoter methylation was negatively correlated with DLC-1 expression in pituitary adenoma (R=-0.67, P=0.01). Conclusion DLC-1 gene promoter methylation is related to the occurrence and development of pituitary adenomas, which can be used as an important indicator for the occurrence of invasive pituitary adenomas.