VEGF/PTEN及下游信号通路在侵袭性垂体瘤中的表达及其临床意义

 目的 探讨侵袭性垂体瘤中血管内皮细胞生长因子(vascular endothelial growth factor, VEGF)与人第10号染色体缺失的磷酸酶 (gene of phosphate and tension homology deleted on chromsome ten, PTEN)表达水平及其下游信号通路的变化的临床意义。方法 收集医院神经外科手术后垂体瘤标本62例(侵袭组32例,非侵袭组30例)和60例正常垂体组织标本(对照组)。通过实时定量PCR和蛋白质印迹法检测比较VEGF、PTEN、磷酸化丝氨酸/苏氨酸激酶(phosphate-Serine/threonine Kinase, p-Akt)、磷酸化丝裂原活化蛋白激酶(phosphate-mitogen-activated protein kinase, p-MAPK)在垂体瘤和正常垂体组织之间的表达差异。结果 垂体瘤标本中VEGF的表达水平显著高于对照组(P<0.05),在侵袭组(3.61±0.16)中的表达高于非侵袭组(2.06±0.13),差异有统计学意义(t=10.60, P<0.05),而PTEN在垂体瘤标本中的表达显著低于对照组(P<0.05),尤其在侵袭组(0.42±0.10)中的表达显著降低(t=6.31, P<0.05)。垂体瘤标本中p-Akt和p-MAPK水平显著高于对照组(P<0.05),且侵袭组(p-Akt 3.90±0.14; p-MAPK 2.52±0.11)明显高于非侵袭组(p-Akt 2.27±0.11; p-MAPK 1.89±0.05)(p-Akt,t=12.95, P<0.05; p-MAPK t=7.29, P<0.05)。结论 侵袭性垂体瘤中VEGF、p-Akt及p-MAPK水平明显增高,而PTEN表达水平显著降低,提示上述变化可能与垂体瘤的侵袭性相关,其可能为诊断并治疗侵袭性垂体瘤靶点的选择提供新方向。

Expressions of VEGF,PTEN, and downstream signaling pathways in invasive pituitary adenomas

Objective To analyze the expressions of vascular endothelial growth factor (VEGF), gene of phosphate and tension homology deleted on chromosome ten (PTEN), and downstream signaling pathways in invasive pituitary adenomas.Methods Sixty-two cases of pituitary adenomas (32 invasive and 30 non-invasive tumors) and 60 cases of normal pituitary glands were selected. The expressions of PTEN/VEGF, their downstream phosphate-serine/threonine kinase (p-Akt) and phosphate-mitogen-activated protein kinase (p-MAPK) signaling pathways in all the pituitary adenomas and normal pituitary glands were detected by quantitative polymerase chain reaction and Western blot.Results (1)There was a significant decrease of PTEN and notable increase of VEGF in patients with pituitary adenomas compared to the normal controls(P<0.05). Meanwhile, the expression levels of PTEN (0.42±0.10)and VEGF(3.61±0.16) in the invasive pituitary adenomas were significantly different from those in the non- invasive pituitary adenomas (PTEN 0.86±0.11, VEGF 2.06±0.13) (PTEN t=6.31,P<0.05; VEGF t=10.60, P<0.05).(2) Levels of p-Akt and p-MAPK in the pituitary adenoma group were notably increased compared with the control group(P<0.05), whereas the invasive pituitary adenomas(p-Akt 3.90±0.14; p-MAPK 2.52±0.11) showed a statistically significant increase compared with the non- invasive pituitary adenomas(p-Akt 2.27±0.11; p-MAPK 1.89±0.05)(p-Akt, t=12.95, P<0.05; p-MAPK t=7.29, P<0.05).Conclusions Our study has offered evidence that there is a significant decrease of PTEN and notable increase of VEGF, p-Akt and p-MAPK in invasive pituitary adenomas, suggesting that these changes may be related to the invasiveness of pituitary adenomas. These findings can facilitate the diagnosis and treatment of invasive pituitary adenomas.