Dong Wei, Zhu Haibo, Gao Hua, Shi Wenjian, Zhang Yu, Wang Hongyun, Li Chuzhong, Song Guidong, Zhang Yazhuo
Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China; Department of Neurosurgery, Tangshan People's Hospital, Tangshan, Hebei, People's Republic of China.
Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China.
World Neurosurg. 2019 Jan;121:e45-e53. doi: 10.1016/j.wneu.2018.08.209. Epub 2018 Sep 6.
The present study was conducted to evaluate the levels of Cdk2, cyclin E, p21, and p27 in growth hormone adenomas (GHPAs) and analyze their association with clinicopathologic features.
We collected 46 GHPA specimens and clinical materials from March 2012 to December 2015 at Beijing Tiantan Hospital. We analyzed the expression of Cdk2, cyclin E, p21, and p27 using immunohistochemistry, quantitative real-time polymerase chain reaction, Western blot, and methylation-specific polymerase chain reaction and sequencing.
The levels of cyclin E and Cdk2 were much greater in the invasive group than in the noninvasive group (P < 0.05). Significant differences were found between cyclin E and p21 and tumor size (P < 0.05) and between cyclin E expression and invasion (P < 0.05). Tumors were more likely to require whole resection in patients with low cyclin E expression (P < 0.05). The high-level p27 group had better progression-free survival than did the low-level p27 group (P < 0.01). Quantitative real-time polymerase chain reaction and Western blot analysis revealed a similar trend for Cdk2, cyclin E, p21, and p27 protein levels in growth hormone specimens (P < 0.01). An average of 33 CpG sites per sample were analyzed using matrix-assisted laser desorption ionization time-of-flight mass array, and in 7 of the 33 CpG sites, the methylation levels of p27 were >50%. Statistically significant differences were found in 4 CpG sites between the invasive and noninvasive specimens (P < 0.01).
Overexpression of cyclin E/Cdk2 and loss of p27 appears to be associated with a poor prognosis and might play a role in the treatment of GHPAs in the future.
本研究旨在评估生长激素腺瘤（GHPA）中细胞周期蛋白依赖性激酶2（Cdk2）、细胞周期蛋白E（cyclin E）、p21和p27的水平，并分析它们与临床病理特征的相关性。
我们于2012年3月至2015年12月在北京天坛医院收集了46例GHPA标本及临床资料。我们采用免疫组织化学、定量实时聚合酶链反应、蛋白质免疫印迹法以及甲基化特异性聚合酶链反应和测序技术分析了Cdk2、cyclin E、p21和p27的表达情况。
侵袭性组中cyclin E和Cdk2的水平显著高于非侵袭性组（P < 0.05）。cyclin E与p21以及肿瘤大小之间（P < 0.05），cyclin E表达与侵袭之间（P < 0.05）均存在显著差异。cyclin E低表达的患者肿瘤更有可能需要进行全切除（P < 0.05）。p27高水平组的无进展生存期优于p27低水平组（P < 0.01）。定量实时聚合酶链反应和蛋白质免疫印迹分析显示生长激素标本中Cdk2、cyclin E、p21和p27蛋白水平呈现相似趋势（P < 0.01）。使用基质辅助激光解吸电离飞行时间质谱阵列分析每个样本平均33个CpG位点，在33个CpG位点中的7个位点，p27的甲基化水平>50%。侵袭性和非侵袭性标本之间在4个CpG位点存在统计学显著差异（P < 0.01）。
cyclin E/Cdk2的过表达和p27的缺失似乎与预后不良相关，并且可能在未来GHPA的治疗中发挥作用。
