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肿瘤相关巨噬细胞亚型在上皮性卵巢癌中的表达及意义
Expression and Significance of Tumor-Associated Macrophage Subtypes in Epithelial Ovarian Cancer
【摘要】 目的通过检测CD68、CD163和HLA-DR在上皮性卵巢癌和卵巢良性肿瘤中的表达,探讨其与上皮性卵巢癌患者临床病理特征及5年生存率的相关性。方法收集2009年8月—2011年12月在湖南省肿瘤医院妇瘤科就诊的41例上皮性卵巢癌患者为观察组,并以同期就诊的17例卵巢良性肿瘤患者为对照组。采用免疫组织化学法检测两组患者的肿瘤相关巨噬细胞(TAMs)标志物(包括M1和M2型)CD68、M1型TAM标志物HLA-DR和M2型TAM标志物CD163的表达水平,分析CD68、HLA-DR、CD163与上皮性卵巢癌患者临床病理参数及预后的关系。结果上皮性卵巢癌患者CD68、CD163表达水平均显著高于卵巢良性肿瘤患者(P<0.05)。以TAMs计数的中位数为界,将CD68、CD163和HLA-DR分为高密度组和低密度组,将CD163/CD68(M2/TAM)的比值以其中位数为界,分为高密度组和低密度组,CD68、CD163及HLADR的表达密度均与年龄无关(P>0.05),CD68高、低密度的表达与组织学分化、病理学类型、临床分期以及有无淋巴结转移显著相关(P<0.05),CD163高、低密度的表达与组织学分化显著相关(P<0.05);CD163/CD68比值的高低与临床分期和组织学分化显著相关(P<0.05)。生存分析显示,不同CD163/CD68比值患者的生存时间比较,差异有统计学意义(P<0.05),CD163/CD68比值较高的患者预后不良。COX多因素分析显示,CD163/CD68比值是影响上皮性卵巢癌患者预后的独立因素(P<0.05)。结论 TAMs可能参与上皮性卵巢癌的发展;CD163/CD68比值可能与上皮性卵巢癌患者的预后相关,降低CD163/CD68比值可能在提高患者生存率方面具有一定的潜力。
【Abstract】 Objective To detect the expression of CD68, CD163 and HLA-DR in epithelial ovarian cancer and benign ovarian tumor, and to investigate its relationship with the clinicopathological features and 5-year survival rate. Methods A total of 41 patients with epithelial ovarian cancer were collected as observation group from Hunan Cancer Hospital between August 2009 and December 2011. Another 17 patients with benign ovarian tumor diagnosed in the same period were selected as the control group. Immunohistochemistry was applied to detect the expressions of CD68(markers of macrophages, including M1 and M2), HLA-DR(markers of M1 macrophages) and CD163(markers of M2 macrophages) in the two groups. The relationship of their positive expressions was also analyzed with the clinicopathological parameters and prognosis of ovarian cancer. Results The expression levels of CD68 and CD163 in epithelial ovarian cancer was significantly higher than in benign ovarian tumor(P<0.05). Taking the median expression level of tumor-associated macrophages(TAMs) as the boundary, there were high density group and low density group of CD68, CD163 and HLA-DR. The ratio of CD163/CD68(M2/TAM) was also taken as the cut-off for high density group and low density group. No correlation was found between the age and the expression density of CD68, CD163 and HLA-DR(P>0.05). But there were statistical differences in histological differentiation, pathological type, clinical stage and lymph node metastasis between the groups with high or low expression density of CD68(P<0.05). In addition, there was a statistical difference in histological differentiation between the groups with high or low expression density of CD163(P<0.05). The ratio of CD163/CD68 was also closely related to clinical stage and histological differentiation(P<0.05). Survival analysis found that there was a statistical difference in survival time between the patients with high or low ratio of CD163/CD68(P<0.05), and that patients with high ratio of CD163/CD68 had poor prognosis. COX multivariate analysis showed that the CD163/CD68 ratio was the independent factor for prognosis of patients with epithelial ovarian cancer(P<0.05). Conclusion TAMs may be involved in the development of epithelial ovarian cancer. The CD163/CD68 ratio may have a relationship with the prognosis of epithelial ovarian cancer patients. By reducing the ratio of CD163/CD68, it is possible to have some potential in improving the survival rate of patients with epithelial ovarian cancer.
【Key words】 Ovarian cancer; Tumor-associated macrophages; Tumor microenvironment; Polarization;
- 【文献出处】 肿瘤药学 ,Anti-tumor Pharmacy , 编辑部邮箱 ,2020年04期
- 【分类号】R737.31
- 【被引频次】3
- 【下载频次】160