乳腺癌患者血清HAS2、CD44水平变化及其临床意义

doi:10.3969/j.issn.1673-8640.2023.05.004

摘要/Abstract

摘要：

目的探讨乳腺癌患者血清透明质酸合成酶2（HAS2）和分化抗原簇44（CD44）水平的变化及其临床意义。方法选取2020年1月—2021年6月上海交通大学医学院附属第六人民医院乳腺癌患者52例（乳腺癌组）、乳腺良性疾病患者40例（乳腺良性疾病组）、健康体检者34名（正常对照组）。收集所有研究对象的临床资料，并检测血清HAS2和CD44水平。采用Pearson相关分析评估HAS2与CD44的相关性。采用受试者工作特征（ROC）曲线评估血清HAS2、CD44、癌胚抗原（CEA）和糖类抗原（CA）15-3单项检测和联合检测诊断乳腺癌的效能。结果正常对照组、乳腺良性疾病组和乳腺癌组血清HAS2和CD44水平依次升高（P<0.000 1）。Pearson相关分析结果显示，正常对照组、乳腺良性疾病组和乳腺癌组血清HAS2与CD44均呈正相关（r值分别为0.364 4、0.415 2、0.290 5，P<0.05）。ROC曲线分析结果显示，血清HAS2、CD44、CEA、CA15-3单项检测和4项指标联合检测诊断乳腺癌的曲线下面积（AUC）分别为0.800、0.805、0.560、0.621、0.883；4项指标联合检测模型诊断早期（TNM分期 Ⅰ~Ⅱ）和晚期（TNM分期 Ⅲ~Ⅳ）乳腺癌的AUC分别为0.860、0.919。不同肿瘤大小、组织学分级、人表皮生长因子受体2（HER2）表达和有无淋巴转移的乳腺癌患者之间血清HAS2水平差异均有统计学意义（P<0.05），不同年龄、雌激素受体（ER）表达、孕激素受体（PR）表达、Ki67表达和有无脉管侵犯的乳腺癌患者之间血清HAS2水平差异均无统计学意义（P>0.05）。不同临床病理特征的乳腺癌患者之间血清CD44水平差异均无统计学意义（P>0.05）。血清HAS2诊断乳腺癌淋巴转移的AUC为0.739。结论 HAS2和CD44可作为乳腺癌的辅助诊断指标。血清HAS2水平与乳腺癌恶性进展密切相关，或可作为预后判断的指标之一。

关键词: 透明质酸合成酶2, 分化抗原簇44, 乳腺癌, 淋巴转移

Abstract:

Objective To investigate the changes of serum hyaluronan synthase 2（HAS2） and differentiated antigen cluster 44（CD44）levels and the clinical values in patients with breast cancer. Methods From January 2020 to June 2021，52 patients with breast cancer（breast cancer group），40 patients with benign breast diseases（benign disease group）and 34 healthy subjects（healthy control group）from Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled. The clinical data were collected，and serum HAS2 and CD44 levels were determined. Pearson correlation analysis was used to evaluate the correlation between serum HAS2 and CD44 levels. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of single and combined determinations of serum HAS2，CD44，carcinoembryonic antigen（CEA） and carbohydrate antigen（CA）15-3 in the diagnosis of breast cancer. Results Serum HAS2 and CD44 in healthy control group，benign disease group and breast cancer group were increased successively（P<0.000 1）. Pearson correlation analysis showed that serum HAS2 and CD44 levels were positively correlated in healthy control group，benign disease group and breast cancer group（r values were 0.364 4，0.415 2 and 0.290 5，respectively，P<0.05）. ROC curve analysis showed that the areas under curves（AUC） of serum HAS2，CD44，CEA and CA15-3 by single and combined determinations in the diagnosis of breast cancer were 0.800，0.805，0.560，0.621 and 0.883，respectively. The AUC of combined determination in the diagnosis of early stage（TNM stage Ⅰ to Ⅱ） and late stage（TNM stage Ⅲ to Ⅳ）were 0.860 and 0.919，respectively. There was statistical significance in serum HAS2 level among breast cancer patients with different tumor sizes，histological grades，human epidermal growth factor receptor 2（HER2） expressions and lymphatic metastasis（P<0.05）. There was no statistical significance in serum HAS2 level among breast cancer patients with different ages，estrogen receptor（ER） expressions，progesterone receptor（PR） expressions，Ki67 expressions and vascular invasions（P>0.05）. There was no statistical significance in serum CD44 level among breast cancer patients with different clinicopathologic characteristics（P>0.05）. The AUC of serum HAS2 in the diagnosis of lymphatic metastasis of breast cancer was 0.739. Conclusions Serum HAS2 and CD44 are potential as auxiliary diagnostic indicators for breast cancer. Serum HAS2 level is related to breast cancer malignant progression，which may be used as one of the prognostic indicators.

Key words: Hyaluronan synthase 2, Differentiated antigen cluster 44, Breast cancer, Lymphatic metastasis

中图分类号:

R446.1

张国良, 刘鷖雯, 何怡青, 许静, 杨翠霞, 高锋, 刘华. 乳腺癌患者血清HAS2、CD44水平变化及其临床意义[J]. 检验医学, 2023, 38(5): 424-429.

ZHANG Guoliang, LIU Yiwen, HE Yiqing, XU Jing, YANG Cuixia, GAO Feng, LIU Hua. Changes of serum HAS2 and CD44 levels in breast cancer patients and their clinical significance[J]. Laboratory Medicine, 2023, 38(5): 424-429.

图/表 7

参考文献 13

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组别	例数	HAS2/（pg/mL）	CD44/（pg/mL）
正常对照组	34	171.1±50.7	504.7±142.9
乳腺良性疾病组	40	203.5±59.1^*	584.8±111.1^**
乳腺癌组	52	238.7±60.7^***#	674.8±145.1^***#
F值		14.41	16.80
P值		<0.000 1	<0.000 1

组别	例数	HAS2/（pg/mL）	CD44/（pg/mL）
正常对照组	34	171.1±50.7	504.7±142.9
乳腺良性疾病组	40	203.5±59.1^*	584.8±111.1^**
乳腺癌组	52	238.7±60.7^***#	674.8±145.1^***#
F值		14.41	16.80
P值		<0.000 1	<0.000 1

指标	AUC（95%CI ^①）	最佳临界值	敏感性/%	特异性/%	P值
HAS2	0.800（0.706~0.894）	154.0 pg/mL	100.00	47.06	<0.000 1
CD44	0.805（0.709~0.901）	519.0 ng/mL	90.38	64.71	<0.000 1
CEA	0.560（0.437~0.683）	1.715 ng/mL	63.46	52.94	0.351 5
CA15-3	0.621（0.500~0.741）	7.840 U/mL	69.23	58.82	0.060 0
HAS2+CD44	0.865（0.785~0.945）	0.617 4	75.00	85.29	<0.000 1
HAS2+CD44+CEA	0.876（0.798~0.954）	0.580 9	84.60	79.41	<0.000 1
HAS2+CD44+CA15-3	0.874（0.800~0.949）	0.572 2	80.80	79.41	<0.000 1
HAS2+CD44+CEA+CA15-3	0.883（0.810~0.956）	0.500 0	90.40	76.47	<0.000 1

指标	AUC（95%CI ^①）	最佳临界值	敏感性/%	特异性/%	P值
HAS2	0.800（0.706~0.894）	154.0 pg/mL	100.00	47.06	<0.000 1
CD44	0.805（0.709~0.901）	519.0 ng/mL	90.38	64.71	<0.000 1
CEA	0.560（0.437~0.683）	1.715 ng/mL	63.46	52.94	0.351 5
CA15-3	0.621（0.500~0.741）	7.840 U/mL	69.23	58.82	0.060 0
HAS2+CD44	0.865（0.785~0.945）	0.617 4	75.00	85.29	<0.000 1
HAS2+CD44+CEA	0.876（0.798~0.954）	0.580 9	84.60	79.41	<0.000 1
HAS2+CD44+CA15-3	0.874（0.800~0.949）	0.572 2	80.80	79.41	<0.000 1
HAS2+CD44+CEA+CA15-3	0.883（0.810~0.956）	0.500 0	90.40	76.47	<0.000 1

临床病理特征	例数	HAS2/（pg/mL）	CD44/（pg/mL）
年龄^①
<49岁	25	254.8±54.3	705.6±146.7
≥49岁	27	223.8±63.5	646.3±140.2
t值		1.866 0	1.493 0
P值		0.065 0	0.142 2
肿瘤直径^①
<2 cm	23	215.9±50.5	672.5±142.0
≥2 cm	29	256.8±62.9	676.6±149.9
t值		2.573 0	0.101 0
P值		0.014 4	0.920 0
组织学分级
Ⅰ~Ⅱ级	33	223.3±51.7	664.4±130.3
Ⅲ级	19	264.8±67.6	692.9±170.0
t值		2.486 0	0.678 4
P值		0.017 1	0.500 6
淋巴转移
无	32	221.2±58.3	67.92±143.4
有	20	266.8±54.9	667.7±151.2
t值		2.864 0	0.274 5
P值		0.007 1	0.784 8
脉管侵犯
无	35	230.8±55.3	681.3±153.9
有	17	254.9±69.6	661.5±128.2
t值		1.354 0	0.458 1
P值		0.181 9	0.648 9
ER
阴性	15	232.8±60.3	681.3±153.9
阳性	37	241.1±61.6	661.5±128.2
t值		0.446 7	0.108 1
P值		0.651 0	0.914 3
PR
阴性	21	234.6±55.8	692.9±142.1
阳性	31	241.5±64.6	662.5±148.1
t值		0.395 1	0.737 8
P值		0.694 4	0.464 1
HER2
阴性	38	226.2±54.0	663.0±153.4
阳性	14	274.9±64.1	706.7±118.7
t值		2.137 0	0.865 6
P值		0.008 1	0.340 8
Ki67
<14%	16	222.4±53.9	650.8±142.2
≥14%	36	246.0±62.9	685.4±147.0
t值		1.099 0	0.939 7
P值		0.198 9	0.432 6