CCL17基因在垂体瘤微环境下的表达及其临床意义

Expression of CCL17 in pituitary adenoma microenvironment and its clinical significance

关键词:  垂体瘤  CCL17  巨噬细胞  肿瘤微环境

Key words:  pituitary tumor  CCL17  macrophages  tumor microenvironment

摘要:

目的　探讨肥胖介导的趋化因子CCL17对垂体腺瘤侵袭性的影响及其临床意义。方法　采用免疫组织化学方法检测64例垂体腺瘤（pituitary adenomas, PAs）组织中巨噬细胞浸润情况，分析巨噬细胞浸润与CCL17表达的相关性。通过免疫荧光和qPCR定量检测侵袭性（32例）和非侵袭性（32例）PAs样本中CCL17的表达水平，评估分析CCL17表达对垂体瘤侵袭进展和不良预后的临床意义。结果　侵袭性PAs中巨噬细胞浸润显著高于非侵袭性垂体瘤（P<005）。免疫荧光和qPCR显示，CCL17的表达在侵袭性垂体瘤中显著增高（P<005），并且与巨噬细胞浸润（r=0307 6,P<005）和肿瘤大小（r=0356 7,P<005）呈显著的正相关性。在CCL17重组蛋白作用下，垂体腺瘤细胞在48和72 h增殖显著增加（P<005），且在72 h迁移能力显著增强（P<005）。根据临床资料的单因素分析，高表达CCL17的患者呈现肿瘤体积更大(P=0023)，侵袭性更强(P=0024)，术后复发的易感程度也越高(P=0031)；CCL17的表达与患者BMI呈正相关性(P=0003)。结论　肥胖介导的趋化因子CCL17高表达可能与PA的侵袭进展及患者肿瘤复发密切相关，检测CCL17对PA患者的预后判断具有参考价值。

Abstract:

Objective　To explore the expression of obesity-mediated chemokine CCL17 in pituitary tumors and its relation with tumor invasion and prognosis. Methods　Immunohistochemical method was used to detect macrophage infiltration in 64 cases of pituitary adenomas（PAs), and the correlation between macrophage infiltration and CCL17 expression was analyzed. The expression level of CCL17 in invasive（32 cases) and non-invasive（32 cases) PA samples was quantitatively determined by immunofluorescence and qPCR. The clinical significance of CCL17 expression in invasion, progression and prognosis of PAs was analyzed. Results　The infiltration of macrophages in invasive PAs was significantly higher than that in non-invasive PAs（P<005). Immunofluorescence and qPCR showed that the expression of CCL17 was significantly increased in aggressive pituitary tumors（P<005), which was positively correlated with macrophage infiltration（r=0307 6,P<005) and tumor size（r=0356 7, P<005). CCK8 and cell migration assay confirmed the promoting effect of CCL17 on the proliferation and migration of pituitary tumor cells. Univariate analysis showed that high expression of CCL17 was significantly associated with larger and more aggressive pituitary tumor（P=0023 and P=0024), and postoperative recurrence（P=0031)，additionally, was associated with BMI of patients. Conclusion　The high expression of obesity-mediated CCL17 protein may be closely related to the invasion and progression of PA and tumor recurrence in patients. Detection of CCL17 protein has reference value for prognosis judgment of PA patients.