Okada Yousuke, Sugita Yasuo, Ohshima Koichi, Morioka Motohiro, Komaki Satoru, Miyoshi Junko, Abe Hideyuki
Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
Department of Neurosurgery, Kurume University School of Medicine, Kurume, Japan.
Neuropathology. 2016 Dec;36(6):535-543. doi: 10.1111/neup.12315. Epub 2016 Jun 14.
Ghrelin is a 28-amino-acid peptide that is the endogenous ligand for the pituitary growth hormone secretagogue receptor (GHS-R). Ghrelin is mainly produced from the stomach, but it is also expressed by various other tissues, including the CNS under normal conditions. Physiologically, ghrelin regulates appetite, gut motility, and GH release from the anterior pituitary, as well as cardiovascular and immune systems. Recent studies also indicate that ghrelin and GHS-R may play an important autocrine/paracrine role in neoplastic conditions. In order to clarify the role of ghrelin/GHS-R in gliomas, the present study assessed the expression of ghrelin and its functional receptor, GHS-R1a, in 39 glioblastomas (GBs), 13 anaplastic astrocytomas (AAs) and 11 diffuse astrocytomas (DAs) using immunohistochemical analyses. Immunohistochemical staining was evaluated as follows: no staining; 1+, 0-10% positive cells; 2+, 10-50% positive cells; 3+, >50% positive cells. Ghrelin expression was detected in 52 of 63 cases of which 38, 13 and one were scored as 3+, 2+ and 1+, respectively. GHS-R1a expression was detected in 45 of 63 cases of which 29, 15 and one were scored as 3+, 2+ and 1+, respectively. Ghrelin immunoreactivity was observed in 38 of 39 GBs, 12 of 13 AAs and two of 11 DAs. GHS-R1a immunoreactivity was observed in 39 of 39 GBs, five of 13 AAs, and one of 11 DAs. AAs and GBs showed moderate or strong immunostaining of ghrelin/GHS-R1a in the tumor cells and in proliferating microvessels. Patients were classified into lower to moderate-score, and high-score ghrelin/GHS-R categories according to the principal component and cluster analyses. Multivariate analysis of overall survival indicated that there was a significant difference (P = 0.0001) in the survival rate between these two groups. The combined results indicated that expression of the ghrelin/GHS-R1a axis increases the growth of AAs and GBs through an autocrine/paracrine mechanism.
胃饥饿素是一种由28个氨基酸组成的肽，是垂体生长激素促分泌素受体（GHS-R）的内源性配体。胃饥饿素主要由胃产生，但在正常情况下，包括中枢神经系统在内的各种其他组织也会表达。在生理上，胃饥饿素调节食欲、肠道蠕动、垂体前叶生长激素的释放，以及心血管和免疫系统。最近的研究还表明，胃饥饿素和GHS-R在肿瘤形成过程中可能发挥重要的自分泌/旁分泌作用。为了阐明胃饥饿素/GHS-R在胶质瘤中的作用，本研究采用免疫组化分析评估了39例胶质母细胞瘤（GBs）、13例间变性星形细胞瘤（AAs）和11例弥漫性星形细胞瘤（DAs）中胃饥饿素及其功能性受体GHS-R1a的表达。免疫组化染色评估如下：无染色；1+，0-10%阳性细胞；2+，10-50%阳性细胞；3+，>50%阳性细胞。在63例病例中的52例检测到胃饥饿素表达，其中38例、13例和1例分别评分为3+、2+和1+。在63例病例中的45例检测到GHS-R1a表达，其中29例、15例和1例分别评分为3+、2+和1+。在39例GBs中的38例、13例AAs中的12例和11例DAs中的2例观察到胃饥饿素免疫反应性。在39例GBs中的每例、13例AAs中的5例和11例DAs中的1例观察到GHS-R1a免疫反应性。AAs和GBs在肿瘤细胞和增殖微血管中显示出胃饥饿素/GHS-R1a的中度或强免疫染色。根据主成分分析和聚类分析，将患者分为低至中度评分和高评分胃饥饿素/GHS-R类别。总生存的多变量分析表明，这两组之间的生存率存在显著差异（P = 0.0001）。综合结果表明，胃饥饿素/GHS-R1a轴的表达通过自分泌/旁分泌机制促进AAs和GBs的生长。
