Role of sialylated haptoglobin for the auxiliary diagnosis of hepatitis B-related hepatocellular carcinoma

doi:10.3969/j.issn.1673-8640.2020.11.015

Abstract

Abstract:

Objective To investigate the role of sialylated haptoglobin（Sia-Hp） in the auxiliary diagnosis of hepatitis B-related hepatocellular carcinoma（HCC）. Methods A total of 236 patients with hepatitis B-related cirrhosis were enrolled,and there were 121 patients with liver cirrhosis and HCC（HCC group） and 115 patients with liver cirrhosis without HCC（liver cirrhosis group）. Totally,107 healthy subjects were enrolled as healthy control group. Lectin enzyme-linked immunosorbent assay（Lectin-ELISA） for determining serum Sia-Hp levels was established. Spearman rank correlation analysis was used to evaluate the correlation between various indicators. Receiver operating characteristic（ROC） curve was used to evaluate the efficiency of Sia-Hp and alpha-fetoprotein（AFP） in diagnosing liver cirrhosis with HCC. Results Serum Sia-Hp levels in HCC,healthy control and liver cirrhosis groups were 1.76（1.32-2.22）,1.60（1.17-1.70） and 0.85（0.11-1.56） AU/mL,respectively,which decreased successively among the 3 groups（P<0.001）. Spearman rank correlation analysis showed that there was no correlation between Sia-Hp and AFP in HCC and liver cirrhosis groups（r=0.09,P>0.05）. In HCC group,serum Sia-Hp levels were related to TNM staging（P<0.05）,but were not related to the presence or absence of MVI and tumor size（P>0.05）. There was no statistical significance in serum Sia-Hp levels between patients with different Child-pugh grades in liver cirrhosis group（P>0.05）. ROC curve analysis results showed that the areas under curves（AUC）of Sia-Hp,AFP and the combined determination model DIAHCC for diagnosing liver cirrhosis with HCC were 0.83,0.78 and 0.92,respectively,and the AUC of patients with liver cirrhosis and HCC by Sia-Hp and the combined determination model DIAHCC for diagnosing AFP negative（AFP<20 μg/L） were 0.84 and 0.88,respectively. Conclusions Serum Sia-Hp may be used as one of the auxiliary diagnostic indicators of liver cirrhosis with HCC.

Key words: Haptoglobin, Sialic acid, Alpha-fetoprotein, Liver cirrhosis, Hepatocellular carcinoma

CLC Number:

R521

BIE Lihan, FANG Meng, FENG Huijuan, LU Zhicheng, GAO Chunfang. Role of sialylated haptoglobin for the auxiliary diagnosis of hepatitis B-related hepatocellular carcinoma[J]. Laboratory Medicine, 2020, 35(11): 1147-1152.

Figures/Tables 5

References 15

[1]	孙可欣,郑荣寿,张思维,等. 2015年中国分地区恶性肿瘤发病和死亡分析[J]. 中国肿瘤,2019,28(1):1-11.
[2]	LIN C L,KAO J H.Risk stratification for hepatitis B virus related hepatocellular carcinoma[J]. J Gastroenterol Hepatol,2013,28(1):10-17.
[3]	TZARTZEVA K,OBI J,RICH N E,et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis:a meta-analysis[J]. Gastroenterology,2018,154(6):1706-1718.e1.
[4]	PINHO S S,REIS C A.Glycosylation in cancer:mechanisms and clinical implications[J]. Nat Rev Cancer,2015,15(9):540-555.
[5]	ISHIKAWA T,YONEYAMA T,TOBISAWA Y,et al.An automated micro-total immunoassay system for measuring cancer-associated α2,3-linked sialyl N-glycan-carrying prostate-specific antigen may improve the accuracy of prostate cancer diagnosis[J]. Int J Mol Sci,2017,18(2):470.
[6]	ZHANG S,SHANG S,LI W,et al.Insights on N-glycosylation of human haptoglobin and its association with cancers[J]. Glycobiology,2016,26(7):684-692.
[7]	中华人民共和国卫生和计划生育委员会医政医管局. 原发性肝癌诊疗规范(2017年版)[J]. 中华消化外科杂志,2017,16(7):635-647.
[8]	王贵强,王福生,成军,等. 慢性乙型肝炎防治指南(2015年版)[J]. 中华实验和临床感染病杂志(电子版),2015,9(5):570-589.
[9]	ZHAO Y,LI Y,MA H,et al.Modification of sialylation mediates the invasive properties and chemosensitivity of human hepatocellular carcinoma[J]. Mol Cell Proteomics,2014,13(2):520-536.
[10]	XU J,LIN Y,WANG Y P,et al.Hepatitis B virus DNA in patients with hepatitis B-related liver cirrhosis with or without hepatocellular carcinomas:a matched case-control study[J]. J Dig Dis,2009,10(2):138-144.
[11]	LI Y,ZHANG Z,SHI J,et al.Risk factors for naturally-occurring early-onset hepatocellular carcinoma in patients with HBV-associated liver cirrhosis in China[J]. Int J Clin Exp Med,2015,8(1):1205-1212.
[12]	ANG I L,POON T C,LAI P B,et al.Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma:a glycoproteomic approach[J]. J Proteome Res,2006,5(10):2691-2700.
[13]	HUANG Y,ZHOU S,ZHU J,et al.LC-MS/MS isomeric profiling of permethylated N-glycans derived from serum haptoglobin of hepatocellular carcinoma(HCC)and cirrhotic patients[J]. Electrophoresis,2017,38(17):2160-2167.
[14]	HAN L L,LV Y,GUO H,et al.Implications of biomarkers in human hepatocellular carcinoma pathogenesis and therapy[J]. World J Gastroenterol,2014,20(30):10249-10261.
[15]	LEI Z,LI J,WU D,et al.Nomogram for Preoperative estimation of microvascular invasion risk in hepatitis B virus-related hepatocellular carcinoma within the Milan criteria[J]. JAMA Surg,2016,151(4):356-363.

组别	例数	年龄/岁	TB/（μmol/L）	TP/（g/L）
HCC组	121	54（48~60）	14.00（10.70~17.50）	69.10（66.20~73.50）
肝硬化组	115	54（48~63）	27.00（14.35~46.00）	64.80（60.50~69.60）
正常对照组	107	27（24~41）	11.20（9.00~14.85）	76.20（73.40~79.00）
H值		128.67	96.50	146.47
P值		<0.05	<0.05	<0.05
组别	ALT/（U/L）	WBC计数/（×10⁹/L）	AFP/（μg/L）	CEA/（μg/L）
HCC组	29.00（21.00~44.00）	4.47（3.74~5.46）	25.90（5.60~645.25）	2.50（1.60~3.30）
肝硬化组	23.00（17.00~43.00）	3.38（1.925~4.85）	3.50（1.80~11.20）	2.80（1.90~4.30）
正常对照组	12.00（9.00~20.00）	6.21（5.31~7.22）	2.40（1.60~3.40）	1.50（1.05~2.35）
H值	80.80	98.00	126.81	49.11
P值	<0.05	<0.05	<0.05	<0.05

组别	例数	年龄/岁	TB/（μmol/L）	TP/（g/L）
HCC组	121	54（48~60）	14.00（10.70~17.50）	69.10（66.20~73.50）
肝硬化组	115	54（48~63）	27.00（14.35~46.00）	64.80（60.50~69.60）
正常对照组	107	27（24~41）	11.20（9.00~14.85）	76.20（73.40~79.00）
H值		128.67	96.50	146.47
P值		<0.05	<0.05	<0.05
组别	ALT/（U/L）	WBC计数/（×10⁹/L）	AFP/（μg/L）	CEA/（μg/L）
HCC组	29.00（21.00~44.00）	4.47（3.74~5.46）	25.90（5.60~645.25）	2.50（1.60~3.30）
肝硬化组	23.00（17.00~43.00）	3.38（1.925~4.85）	3.50（1.80~11.20）	2.80（1.90~4.30）
正常对照组	12.00（9.00~20.00）	6.21（5.31~7.22）	2.40（1.60~3.40）	1.50（1.05~2.35）
H值	80.80	98.00	126.81	49.11
P值	<0.05	<0.05	<0.05	<0.05