血浆HA与外周血M2型单核细胞/M1型单核细胞比值联合检测在乳腺癌中的临床应用价值

doi:10.3969/j.issn.1673-8640.2019.02.005

摘要/Abstract

摘要：

目的探讨血浆透明质酸（HA）与外周血M2型单核细胞/M1型单核细胞比值（简称M2/M1比值）联合检测在乳腺癌中的临床应用价值。方法选取98例乳腺癌患者（乳腺癌组）、37例乳腺良性疾病患者（乳腺良性疾病组）和41名体检健康者（正常对照组）。采用化学发光法检测血浆HA和糖类抗原（CA）15-3水平;采用流式细胞术检测外周血M1型（CD14⁺CD163^-CD86⁺）和M2型（CD14⁺CD163⁺CD204⁺）单核细胞的表达,并计算M2/M1比值。各项指标之间的相关性分析采用Spearman相关分析。采用受试者工作特征（ROC）曲线分析各项指标的诊断效能。结果乳腺癌组血浆HA、CA15-3水平及M2型单核细胞比例、M2/M1比值均明显高于乳腺良性疾病组及正常对照组（P<0.05）,而乳腺良性疾病组与正常对照组之间差异均无统计学意义（P>0.05）。HA与M2/M1比值、M2型单核细胞比例、M1型单核细胞比例均相关（r_s值分别为0.401、0.393、-0.189,P<0.05）。M2/M1比值诊断乳腺癌的曲线下面积（AUC）、敏感性和特异性均高于其他指标,且HA与M2/M1比值联合检测可提高对乳腺癌的诊断效能。血浆HA与乳腺癌组织学分化情况有关（P<0.05）,M2/M1比值与乳腺癌TNM分期、淋巴结转移、组织学分化情况及雌激素受体（ER）均有关（P<0.05）,CA15-3与乳腺癌临床病理特征均无关（P>0.05）。结论 HA与M2/M1比值联合检测对辅助诊断乳腺癌具有一定的临床价值。

关键词: 透明质酸, 肿瘤相关巨噬细胞, 糖类抗原15-3, 乳腺癌

Abstract:

Objective To investigate the role of the combined determination of plasma hyaluronan（HA） and the ratio of M2 monocyte/M1 monocyte（M2/M1 ratio） in breast cancer. Methods A total of 98 patients with breast cancer（breast cancer group）,37 patients with breast benign diseases（breast benign disease group） and 41 healthy subjects（healthy control group） were enrolled. Plasma HA and carbohydrate antigen（CA）15-3 levels were determined by chemiluminescence. Flow cytometry was used to assess the expression of M1（CD14⁺CD163^-CD86⁺） and M2（CD14⁺CD163⁺CD204⁺） monocytes,and M2/M1 ratio was calculated. Correlation analysis was performed using Spearman correlation analysis. Receiver operating characteristic（ROC） curve was used to analyze the diagnostic efficiency of each marker. Results Plasma HA and CA15-3 levels,the proportion of M2 monocyte and M2/M1 ratio were higher in breast cancer group than those in breast benign disease and healthy control groups（P<0.05）,and there was no statistical significance between breast benign disease and healthy control groups（P>0.05）. There were correlations of HA with M2/M1 ratio and the proportions of M2 monocyte and M1 monocyte（r_s=0.401,0.393 and-0.189,P<0.05）. The area under ROC curve（AUC）,sensitivity and specificity of M2/M1 ratio for the diagnosis of breast cancer were higher than those of the other markers,and the combined determination of HA and M2/M1 ratio could improve the diagnostic efficiency of breast cancer. Plasma HA was correlated with the histological differentiation of breast cancer（P<0.05）,and M2/M1 ratio was correlated with tumor-node-metastasis（TNM） stage,histological differentiation,lymph node metastasis and estrogen receptor（ER）（P<0.05）. However,there was no relationship between CA15-3 and clinicopathological characteristics（P>0.05）. Conclusions The combined determination of HA and M2/M1 ratio plays a role in the auxiliary diagnosis of breast cancer.

Key words: Hyaluronan, Tumor-associated macrophage, Carbohydrate antigen 15-3, Breast cancer

中图分类号:

R446.1

张波克, 黄宜, 刘鷖雯, 何怡青, 杨翠霞, 杜艳, 张国良, 高锋. 血浆HA与外周血M2型单核细胞/M1型单核细胞比值联合检测在乳腺癌中的临床应用价值[J]. 检验医学, 2019, 34(2): 116-121.

ZHANG Boke, HUANG Yi, LIU Yiwen, HE Yiqing, YANG Cuixia, DU Yan, ZHANG Guoliang, GAO Feng. Combined determination of plasma hyaluronan and the ratio of M2 monocyte/M1 monocyte ratio in breast cancer[J]. Laboratory Medicine, 2019, 34(2): 116-121.

图/表 5

参考文献 14

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组别	例数	年龄（岁）	白细胞（×10⁹/L）	单核细胞（×10⁹/L）	HA（ng/mL）
乳腺癌组	98	50.50±10.19	5.79±1.65	0.35±0.10	71.25（55.79~96.08）
乳腺良性疾病组	37	49.35±8.26	5.86±1.18	0.36±0.13	49.36（43.83~56.13）^*
正常对照组	41	49.52±9.78	5.28±1.22	0.32±0.11	48.70（45.82~54.64）^*
组别	CA15-3（U/mL）		M1型单核细胞比例（%）	M2型单核细胞比例（%）	M2/M1比值
乳腺癌组	11.06（7.82~16.30）		30.85±5.52^#	5.71±1.52	0.193±0.070
乳腺良性疾病组	8.15（6.64~11.82）^*		39.11±4.97	3.90±0.98^*	0.087±0.028^*
正常对照组	9.82（6.75~12.09）^*		32.58±5.31^#	3.76±1.22^*	0.103±0.035^*

组别	例数	年龄（岁）	白细胞（×10⁹/L）	单核细胞（×10⁹/L）	HA（ng/mL）
乳腺癌组	98	50.50±10.19	5.79±1.65	0.35±0.10	71.25（55.79~96.08）
乳腺良性疾病组	37	49.35±8.26	5.86±1.18	0.36±0.13	49.36（43.83~56.13）^*
正常对照组	41	49.52±9.78	5.28±1.22	0.32±0.11	48.70（45.82~54.64）^*
组别	CA15-3（U/mL）		M1型单核细胞比例（%）	M2型单核细胞比例（%）	M2/M1比值
乳腺癌组	11.06（7.82~16.30）		30.85±5.52^#	5.71±1.52	0.193±0.070
乳腺良性疾病组	8.15（6.64~11.82）^*		39.11±4.97	3.90±0.98^*	0.087±0.028^*
正常对照组	9.82（6.75~12.09）^*		32.58±5.31^#	3.76±1.22^*	0.103±0.035^*

项目	AUC（95%可信区间）	最佳临界值	敏感性（%）	特异性（%）
HA	0.849（0.787~0.911）	61.15 ng/mL	61.22	95.12
CA15-3	0.638（0.544~0.732）	13.67 U/mL	35.71	92.68
M1型单核细胞比例	0.599（0.495~0.703）	35.35%	82.65	41.46
M2型单核细胞比例	0.852（0.779~0.923）	4.99%	71.43	87.80
M2/M1比值	0.909（0.860~0.957）	0.138	80.60	85.37
HA+ M2/M1比值联合检测	0.952（0.918~0.987）		90.82	92.68

项目	AUC（95%可信区间）	最佳临界值	敏感性（%）	特异性（%）
HA	0.849（0.787~0.911）	61.15 ng/mL	61.22	95.12
CA15-3	0.638（0.544~0.732）	13.67 U/mL	35.71	92.68
M1型单核细胞比例	0.599（0.495~0.703）	35.35%	82.65	41.46
M2型单核细胞比例	0.852（0.779~0.923）	4.99%	71.43	87.80
M2/M1比值	0.909（0.860~0.957）	0.138	80.60	85.37
HA+ M2/M1比值联合检测	0.952（0.918~0.987）		90.82	92.68

项目	AUC（95%可信区间）	最佳临界值	敏感性（%）	特异性（%）
HA	0.839（0.772~0.905）	61.17 ng/mL	60.20	89.19
CA15-3	0.631（0.529~0.733）	13.70 U/mL	34.68	83.78
M1型单核细胞比例	0.870（0.808~0.931）	35.69%	85.71	75.68
M2型单核细胞比例	0.851（0.785~0.918）	5.00%	69.39	86.49
M2/M1比值	0.960（0.911~0.984）	0.127	89.80	91.89
HA+ M2/M1比值联合检测	0.973（0.949~0.997）		91.84	97.30