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CD14+HLA-DRLow/-髓源抑制性细胞样细胞与白细胞介素1β在卵巢癌中的表达及相关性

The expression and association of CD14 + HLA-DRLow/-myeloid-derived suppressor cell-like cells and interleukin-1β in ovarian cancer

摘要:

目的 分析卵巢癌患者外周血及腹水CD14+ HLA-DRLow/-髓源抑制性细胞(MDSCs)样细胞与白细胞介素1β(IL-1β)的表达水平,探讨与卵巢癌临床病理特征的相关性.方法 收集2016年1至12月山东大学齐鲁医院31例卵巢癌患者外周血,从中选取5例中晚期患者留取腹腔积液.收集同一时期年龄构成相匹配的20名健康志愿者外周血作为对照.流式细胞术分析卵巢癌患者外周血、腹腔积液以及健康对照者外周血中CD14+ HLA-DRLow/-细胞亚群在CD14+单核细胞中所占比例并分离获取该群细胞.流式细胞术分析CD14+ HLA-DRLow/-细胞亚群表型,实时定量PCR检测该群细胞免疫抑制因子表达情况.酶联免疫吸附法检测卵巢癌患者外周血、腹腔积液以及健康对照者外周血中IL-1 β表达水平,并与CD14+ HLA-DRLow/-细胞所占比例进行相关性分析.统计卵巢癌患者临床资料,分析CD14+ HLA-DRLow/-细胞及IL-1β水平与临床病理特征的相关性.结果 健康对照组及卵巢癌患者外周血CD14+ HLA-DRLow/-细胞在CD14+单核细胞中所占比例分别为(2.30±0.49)%和(3.74±0.95)%,差异有统计学意义(t =6.96,P<0.01),该群细胞表型与因子表达与单核样MDSCs相似.卵巢癌患者腹腔积液中CD14+ HLA-DRLow/-细胞百分比为(16.60±7.35)%,显著高于外周血的(4.03±0.94)%,差异有统计学意义(t =3.87,P<0.05).健康对照组及卵巢癌患者外周血IL-1β水平分别为3.88(0.41,7.07) ng/L及(12.77±3.52) ng/L,差异有统计学意义(Z=-4.93,P<0.01).5例卵巢癌患者腹腔积液IL-1β水平为(62.17 ±23.05) ng/L,显著高于外周血的(12.65 ±3.93) ng/L,差异有统计学意义(=5.20,P<0.01).卵巢癌患者外周血及腹腔积液IL-1β表达水平与CD14+ HLA-DRLow/-细胞比例存在相关性(外周血R2 =0.36,P<0.01;腹腔积液R2=0.68,P<0.05),健康对照组外周血IL-1β表达水平与CD14+ HLA-DRLow/-细胞比例无相关性(R2=0.02,P>0.05).CD14+ HLA-DRLow/-细胞及IL-1β水平与卵巢癌浸润转移及FIGO分期有关.结论 卵巢癌患者CD14+ HLA-DRLow/-细胞及IL-1β存在异常表达,可能与卵巢癌的发展有关.

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abstracts:

Objective To analyze the percentage of CDi4+ HLA-DRLow/-myeloid-derived suppressor cell-like cell subtypes(MDSCs) and interleukin-1 β(IL-1 β) concentration in peripheral blood and ascites of ovarian cancer patients,and to explore their association with clinicopathological characteristics.Methods Blood samples of 31 patients and ascites of 5 patients in Qilu Hospital of Shandong University from January 2016 to December 2016 were collected.Blood samples of 20 healthy volunteers with matched age were collected as control.The percentages of CD14 + HLA-DRLow/-cell subtypes in CD14 + monocytes were collected by flow cytometry and their phenotypes were analyzed.qRT-PCR was used to analyze the expression of immunosuppression factors in this subtype.ELISA was used to analyze IL-1β concentration in peripheral blood and ascites of ovarian cancer patients and healthy controls.The correlation between CD14 + HLA-DRLow/-cell percentage and IL-1β concentration was explored.The association between CD14 + HLA-DRLow/ cell percentage,IL-1β concentration and clinicopathological characteristics were analyzed.Results The percentage of CD14 + HLA-DRLow/-cells in CD14 + monocytes of peripheral blood of healthy controls was (2.30± 0.49)%,and the percentage in ovarian cancer patients was (3.74 ± 0.95)%,with statistical significance (t =6.96,P < 0.01).This cell subset showed similar phenotypes and factor expression with monocytic MDSCs.The percentage of CD14 + HLA-DRLow/ cells in peripheral blood ascites of ovarian cancer patients was (16.60 ± 7.35) %,significantly higher than those in peripheral bloods (4.03 ± 0.94) % (t =3.87,P <0.05).The concentration of IL-1β in peripheral blood of healthy controls was [3.88 (0.41,7.07)] ng/L,and the concentration in ovarian cancer patients was (12.77 ± 3.52) ng/L,with statistical significance (Z =-4.93,P < 0.01).IL-1β concentration in ascites of ovarian cancer patients was (62.17 ± 23.05) ng/L,significantly higher than that in peripheral bloods (12.65 ± 3.93) ng/L(t =5.20,P <0.01).IL-1β concentration was correlated with CD14+ HLA-DRLow/-cell percentage in ovarian cancer patients (R2 =0.36 in peripheral blood,P < 0.01;R2 =0.68 in ascites,P < 0.05),but not in healthy controls (R2 =0.02,P > 0.05).The percentage of CD14 + HLA-DRLow/-cells and IL-1β concentration were associated with metastasis and FIGO stage of ovarian cancer.Conclusion The elevated percentage of CD14 + HLA-DRLow/-cells and IL-1β concentration might involve in the development of ovarian cancer.

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作者: 王华阳 [1] 赵睿 [1] 任浩 [1] 邹明瑾 [1] 张建 [1] 张义 [1]
期刊: 《中华医学杂志》2017年97卷34期 2663-2669页 MEDLINEISTICPKUCSCD
栏目名称: 肿瘤实验室检测
DOI: 10.3760/cma.j.issn.0376-2491.2017.34.005
发布时间: 2017-09-26
基金项目:
山东省重点研发计划 山东省重点研发计划(产业关键技术) 山东大学横向课题(26010111671703)Key Research Program of Shandong Province Key Research Program (key industrial technology) of Shandong Province Transverse Issue of Shandong University
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