血清HYAL1、HA在结直肠癌辅助诊断和疗效监测中的价值

doi:10.3969/j.issn.1673-8640.2023.04.003

摘要/Abstract

摘要：

目的探讨结直肠癌患者血清透明质酸降解酶1（HYAL1）和透明质酸（HA）水平变化及其临床价值。方法选取结直肠癌患者75例（结直肠癌组）、结直肠良性疾病患者46例（良性疾病组）和体检健康者51名（正常对照组）。收集所有研究对象的临床资料，并检测血清HYAL1和HA水平。另检测41例结直肠癌患者术后血清HYAL1和HA水平。采用Pearson相关分析评估各项指标之间的相关性。采用受试者工作特征（ROC）曲线评价血清HYAL1、HA、癌胚抗原（CEA）和糖类抗原19-9（CA19-9）单项和联合检测诊断结直肠癌的效能。结果正常对照组、良性疾病组和结直肠癌组血清HYAL1水平依次升高（P<0.000 1）。结直肠癌组血清HA水平显著高于正常对照组（P<0.000 1），良性疾病组与正常对照组之间、良性疾病组与结直肠癌组之间血清HA水平差异均无统计学意义（P>0.05）。Pearson相关分析结果显示，正常对照组、良性疾病组和结直肠癌组HYAL1与HA均无相关性（r值分别为0.147、0.072、-0.029，P>0.05）。ROC曲线分析结果显示，HYAL1、HA、CEA和CA19-9诊断结直肠癌的曲线下面积（AUC）分别为0.899、0.723、0.717和0.669，HYAL1分别与CEA、CA19-9两两联合和3项联合检测诊断结直肠癌的AUC分别为0.917、0.905和0.916。HYAL1、CEA和CA19-9单项和3项联合检测诊断早期（TNM分期Ⅰ~Ⅱ期）结直肠癌的AUC为0.860、0.686、0.685和0.885。血清HYAL1水平与结直肠癌患者TNM分期、淋巴转移、脉管侵犯和神经侵犯有关（P<0.001）。结直肠癌患者术后血清HYAL1、HA和CEA水平显著低于术前（P<0.01），其中HYAL1的降低幅度最为明显。血清CA19-9水平术前、术后差异无统计学意义（P>0.05）。结论血清HYAL1或可作为早期结直肠癌辅助诊断和疗效监测的血清学指标。

关键词: 透明质酸降解酶1, 透明质酸, 结直肠癌, 辅助诊断, 疗效监测

Abstract:

Objective To investigate the levels of serum hyaluronidase 1（HYAL1） and hyaluronan（HA） and their clinical values in patients with colorectal cancer. Methods Totally，51 healthy subjects（healthy control group），46 patients with colorectal benign lesions（benign lesion group） and 75 colorectal cancer patients（colorectal cancer 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 HYAL1 and HA levels were determined. Serum HYAL1 and HA levels were determined in 41 patients with colorectal cancer after surgery. Pearson correlation analysis was used to evaluate the correlation among all the indicators. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of single and combined determination of serum HYAL1，HA，carcinoembryonic antigen（CEA） and carbohydrate antigen 19-9（CA19-9） in the diagnosis of colorectal cancer. Results Serum HYAL1 levels in healthy control group，benign lesion group and colorectal cancer group were increased successively（P<0.000 1）. The serum HA level in colorectal cancer group was higher than that in healthy control group （P<0.000 1），but there was no statistical significance in serum HA level between benign lesion group and healthy control group，or between benign lesion group and colorectal cancer group（P>0.05）. Pearson correlation analysis showed that there was no correlation between HYAL1 and HA in healthy control group，benign lesion group and colorectal cancer group（r values were 0.147，0.072 and -0.029，P>0.05）. The areas under curves（AUC） of HYAL1，HA，CEA and CA19-9 in the diagnosis of colorectal cancer were 0.899，0.723，0.717 and 0.669，respectively. The AUC of HYAL1 combined with CEA and CA19-9 were 0.917，0.905 and 0.916，respectively. The AUC of HYAL1，CEA and CA19-9 single and combined determinations were 0.860，0.686，0.685 and 0.885 in the diagnosis of early stage（TNM stage Ⅰ to Ⅱ） colorectal cancer. Serum HYAL1 levels were related with TNM stage，lymph metastasis，vascular invasion and nerve invasion in patients with colorectal cancer（P<0.001）. The levels of serum HYAL1，HA and CEA in patients with colorectal cancer after surgery were lower than those before surgery（P<0.01），and the decrease of HYAL1 was the most obvious. There was no statistical significance in serum CA19-9 before and after surgery（P>0.05）. Conclusions Serum HYAL1 may be used as a serological indicator for the auxiliary diagnosis of early colorectal cancer and efficacy monitoring.

Key words: Hyaluronidase 1, Hyaluronan, Colorectal cancer, Auxiliary diagnosis, Therapeutic efficacy monitoring

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. 血清HYAL1、HA在结直肠癌辅助诊断和疗效监测中的价值[J]. 检验医学, 2023, 38(4): 313-319.

ZHANG Guoliang, LIU Yiwen, HE Yiqing, XU Jing, YANG Cuixia, GAO Feng, LIU Hua. Roles of serum HYAL1 and HA in the auxiliary diagnosis and therapeutic monitoring of colorectal cancer[J]. Laboratory Medicine, 2023, 38(4): 313-319.

图/表 8

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组别	例数	HYAL1/（pg/mL）	HA/（ng/mL）
正常对照组	51	880.80±453.60	55.32±10.38
良性疾病组	46	1 530.00±698.80^**	61.35±18.13
炎症组	15	1 927.00±593.40^*	57.81±13.55
腺瘤组	18	1 526.00±606.00^*	64.72±21.27
息肉组	13	1 077.00±693.00	60.77±18.56
结直肠癌组	75	2 148.00±930.90^**#	68.26±19.32^**
结肠癌组	41	2 067.00±956.30^**#	68.62±17.15^**
直肠癌组	34	2 246.00±852.30^**#	67.83±21.91^**

组别	例数	HYAL1/（pg/mL）	HA/（ng/mL）
正常对照组	51	880.80±453.60	55.32±10.38
良性疾病组	46	1 530.00±698.80^**	61.35±18.13
炎症组	15	1 927.00±593.40^*	57.81±13.55
腺瘤组	18	1 526.00±606.00^*	64.72±21.27
息肉组	13	1 077.00±693.00	60.77±18.56
结直肠癌组	75	2 148.00±930.90^**#	68.26±19.32^**
结肠癌组	41	2 067.00±956.30^**#	68.62±17.15^**
直肠癌组	34	2 246.00±852.30^**#	67.83±21.91^**

指标	AUC（95% CI^①）	最佳临界值	敏感性/%	特异性/%	漏诊率/%	误诊率/%	P值
HYAL1	0.899（0.846~0.951）	1 483.00 pg/mL	77.33	90.20	22.67	9.80	<0.000 1
HA	0.723（0.636~0.811）	64.91 ng/mL	56.00	84.31	44.00	15.69	<0.000 1
CEA	0.717（0.629~0.806）	3.13 ng/mL	57.33	86.27	42.67	13.73	<0.000 1
CA19-9	0.669（0.572~0.766）	12.83 U/ mL	52.00	88.24	48.00	11.76	0.001 3
HYAL1+CEA	0.917（0.870~0.964）	0.73	76.00	96.10	24.00	3.90	<0.000 1
HYAL1+CA19-9	0.905（0.854~0.957）	0.58	82.70	88.20	17.30	11.80	<0.000 1
HYAL1+CEA+CA19-9	0.916（0.868~0.964）	0.78	74.70	98.00	25.30	2.00	<0.000 1

指标	AUC（95% CI^①）	最佳临界值	敏感性/%	特异性/%	漏诊率/%	误诊率/%	P值
HYAL1	0.899（0.846~0.951）	1 483.00 pg/mL	77.33	90.20	22.67	9.80	<0.000 1
HA	0.723（0.636~0.811）	64.91 ng/mL	56.00	84.31	44.00	15.69	<0.000 1
CEA	0.717（0.629~0.806）	3.13 ng/mL	57.33	86.27	42.67	13.73	<0.000 1
CA19-9	0.669（0.572~0.766）	12.83 U/ mL	52.00	88.24	48.00	11.76	0.001 3
HYAL1+CEA	0.917（0.870~0.964）	0.73	76.00	96.10	24.00	3.90	<0.000 1
HYAL1+CA19-9	0.905（0.854~0.957）	0.58	82.70	88.20	17.30	11.80	<0.000 1
HYAL1+CEA+CA19-9	0.916（0.868~0.964）	0.78	74.70	98.00	25.30	2.00	<0.000 1

指标	AUC（95%CI）	最佳临界值	敏感性/%	特异性/%	P值
HYAL1	0.860（0.786~0.934）	1 787.00 pg/mL	69.57	90.20	<0.000 1
CEA	0.686（0.576~0.796）	3.13 ng/mL	56.52	84.31	0.001 6
CA19-9	0.685（0.566~0.804）	16.30 U/ mL	45.65	100.00	0.001 7
HYAL1 + CEA + CA19-9	0.885（0.817~0.953）	0.74	65.22	98.04	<0.000 1