Wang Jianpeng, Liu Qian, Gao Hua, Wan Dehong, Li Chuzhong, Li Zhaojian, Zhang Yazhuo
1 Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
2 Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Tumour Biol. 2017 Jul;39(7):1010428317706203. doi: 10.1177/1010428317706203.
Growth hormone-secreting pituitary adenoma accounts for about 20% of the third most common intracranial neoplasm-pituitary adenomas-which makes up 15% of all intracranial tumors. The growth hormone-secreting pituitary adenoma invasion is a key risk factor associated with the operation results and highly correlated with the clinical prognosis. The epidermal growth factor-like domain multiple 7 protein, a unique 29 kDa secreted angiogenic factor, can result in pathologic angiogenesis and enhance the tumor migration and invasion. In this study, for the first time we found that epidermal growth factor-like domain multiple 7 protein expression was markedly higher in invasive growth hormone-secreting pituitary adenoma than non-invasive growth hormone-secreting pituitary adenoma. The tumor volume, histologic subtypes, invasiveness and recurrence of growth hormone-secreting pituitary adenoma were significantly associated with epidermal growth factor-like domain multiple 7 protein expression. Furthermore, we discovered that the histological classification methods of growth hormone-secreting pituitary adenoma according to electron microscopic examination and biological marker classification methods according to epidermal growth factor-like domain multiple 7 protein expression are more valuable in clinical application than the traditional classification methods based on Knosp and Hardy-Wilson grades. In summary, our results indicated epidermal growth factor-like domain multiple 7 protein participates in growth hormone-secreting pituitary adenoma proliferation and invasion regulation via Notch2/DLL3 signaling pathway. These findings raised the possibility that epidermal growth factor-like domain multiple 7 protein might serve as a useful biomarker to assess growth hormone-secreting pituitary adenoma invasion and prognosis or a potential therapeutic target for growth hormone-secreting pituitary adenoma treatment.
分泌生长激素的垂体腺瘤约占第三常见的颅内肿瘤——垂体腺瘤的20%，而垂体腺瘤占所有颅内肿瘤的15%。分泌生长激素的垂体腺瘤侵袭是与手术结果相关的关键危险因素，且与临床预后高度相关。表皮生长因子样结构域多重7蛋白是一种独特的29 kDa分泌型血管生成因子，可导致病理性血管生成并增强肿瘤迁移和侵袭。在本研究中，我们首次发现表皮生长因子样结构域多重7蛋白在侵袭性分泌生长激素的垂体腺瘤中的表达明显高于非侵袭性分泌生长激素的垂体腺瘤。分泌生长激素的垂体腺瘤的肿瘤体积、组织学亚型、侵袭性和复发与表皮生长因子样结构域多重7蛋白表达显著相关。此外，我们发现根据电子显微镜检查的分泌生长激素的垂体腺瘤组织学分类方法以及根据表皮生长因子样结构域多重7蛋白表达的生物标志物分类方法在临床应用中比基于Knosp和Hardy-Wilson分级的传统分类方法更有价值。总之，我们的结果表明表皮生长因子样结构域多重7蛋白通过Notch2/DLL3信号通路参与分泌生长激素的垂体腺瘤的增殖和侵袭调节。这些发现增加了表皮生长因子样结构域多重7蛋白可能作为评估分泌生长激素的垂体腺瘤侵袭和预后的有用生物标志物或分泌生长激素的垂体腺瘤治疗的潜在治疗靶点的可能性。
