细胞周期蛋白依赖性激酶1（CDK1）和极光激酶A（AURKA）在HBV相关肝细胞癌患者血清中的表达及意义

何燕芳; 谢娇娇; 郑兰兰; 郭才; 马燕花

doi:10.12449/JCH240717

细胞周期蛋白依赖性激酶1（CDK1）和极光激酶A（AURKA）在HBV相关肝细胞癌患者血清中的表达及意义

DOI: 10.12449/JCH240717

何燕芳^{1, 2},
谢娇娇^{1, 2},
郑兰兰¹,
郭才¹,
马燕花^1, , ,

1.
甘肃中医药大学第一临床医学院，兰州 730000
2.
甘肃省人民医院消化内科，兰州 730000

基金项目:

国家自然科学基金 (818615010);

甘肃省优秀研究生“创新之星”项目 (2023CXZX-754)

伦理学声明：本研究方案于2022年5月24日经由甘肃省人民医院伦理委员会审批，批号：2022-W001，所纳入患者均签署知情同意书。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：何燕芳负责课题设计，实验实施，收集数据，资料分析，撰写论文；谢娇娇参与采集数据，分析数据；郭才、郑兰兰参与统计分析；马燕花参与课题设计，审核论文并对论文负责。

详细信息

通信作者:
马燕花， 617747928@ qq.com （ORCID： 0009-0000-2240-6413）

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出版历程
- 收稿日期: 2023-10-17
- 录用日期: 2024-01-16
- 出版日期: 2024-07-25

Expression and clinical significance of cell cycle protein-dependent kinase 1 and aurora kinase A in the serum of patients with hepatitis B virus-related hepatocellular carcinoma

Yanfang HE^{1, 2},
Jiaojiao XIE^{1, 2},
Lanlan ZHENG¹,
Cai GUO¹,
Yanhua MA^{1
, ,
,}

1.
The First Clinical Medical College of Gansu University of Chinese Medicine，Lanzhou 730000，China
2.
Department of Gastroenterology，Gansu Provincial Hospital，Lanzhou 730000，China

Research funding:

National Natural Science Foundation of China (818615010);

Gansu Provincial Outstanding Graduate Student “Star of Innovation” Project (2023CXZX-754)

More Information

Corresponding author: MA Yanhua， 617747928@ qq.com （ORCID： 0009-0000-2240-6413）

摘要

摘要: 目的探讨血清细胞周期蛋白依赖性激酶1（CDK1）和极光激酶A（AURKA）在HBV相关肝细胞癌（HBV-HCC）患者中的诊断价值。方法收集2022年6月—2023年12月在甘肃省人民医院消化内科住院部的HBV-HCC患者、HBV相关肝硬化患者（HBV-LC）及慢性乙型肝炎患者（CHB）各50例，收集同期体检中心与病例组年龄、性别相匹配的健康人群50例，记录患者的年龄、性别、并发症以及入院后首次的血常规、肝功能、凝血等检验指标。ELISA法检测各组血清中CDK1和AURKA水平。符合正态分布的计量资料多组间比较采用单因素方差分析，进一步两两比较采用LSD-t检验；非正态分布的计量资料多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Bonferroni检验。计数资料组间比较采用χ²检验或Fisher确切概率法。CDK1与AURKA表达的关系采用Spearman相关分析；受试者工作特征曲线（ROC曲线）下面积（AUC）分析CDK1与AURKA对HBV-HCC的诊断价值。结果与对照组相比，HBV-HCC患者肝功能各项指标差异均有统计学意义（P值均<0.05）；CHB组与HBV-HCC组Alb、Glb、DBil、AST、GGT、ALP水平比较差异均有统计学意义（P值均<0.05）；HBV-LC组与HBV-HCC组Glb、AST、GGT水平比较差异均有统计学意义（P值均<0.05）。HBV-HCC组患者血清中CDK1及AURKA水平明显高于HBV-LC组、CHB组和对照组（P值均<0.05）。CDK1水平与AURKA在总研究人群和HBV-HCC患者中均存在显著的正相关性（r值分别为0.526 6、0.815 2，P值均<0.001）。以对照组为参照，CDK1诊断HBV-HCC的AUC为0.832 3，敏感度为92.86%，特异度为75%；AURKA诊断HCC的AUC为0.886 6，敏感度为95.80%，特异度为74%。以CHB组为参照，CDK1诊断HBV-HCC的AUC为0.833 3，敏感度为93.75%，特异度为75%；AURKA诊断HBV-HCC的AUC为0.972 7，敏感度为95.83%，特异度为91.67%。以HBV-LC组为参照，CDK1诊断HBV-HCC的AUC为0.608 5，敏感度为66.67%，特异度为54.17%；AURKA诊断HBV-HCC的AUC为0.762 2，敏感度为95.83%，特异度为47.92%。结论血清CDK1与AURKA水平随着HBV相关慢性肝病的进展而升高，二者对HBV相关HCC有一定的诊断价值。
- 癌，肝细胞 /
- 细胞周期蛋白质依赖激酶类 /
- 极光激酶A
Abstract: Objective To investigate the value of serum cell cycle protein-dependent kinase 1 （CDK1） and aurora kinase A （AURKA） in the diagnosis of patients with hepatitis B virus-related hepatocellular carcinoma （HBV-HCC）. Methods A total of 50 HBV-HCC patients， 50 patients with hepatitis B virus-related liver cirrhosis （HBV-LC）， and 50 chronic hepatitis B （CHB） patients who were hospitalized in Department of Gastroenterology， Gansu Provincial Hospital， from June 2022 to December 2023 were enrolled， and 50 healthy individuals， matched for age and sex， who received physical examination at Physical Examination Center during the same period of time were enrolled as control group. Related data were recorded for all patients， including age， sex， complications， and the results of routine blood test， liver function， and coagulation for the first time after admission. ELISA was used to measure the serum levels of CDK1 and AURKA. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and the least significant difference Bonferroni test was used for further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation between CDK1 and AURKA， and the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to investigate the value of CDK1 and AURKA in the diagnosis of HBV-HCC. Results There were significant differences in liver function parameters between the HBV-HCC patients and the control group （all P<0.05）； there were significant differences between the CHB group and the HBV-HCC group in albumin， Glb， direct bilirubin， aspartate aminotransferase （AST）， gamma-glutamyl transpeptidase （GGT）， and alkaline phosphatase （all P<0.05）； there were significant differences between the HBV-LC group and the HBV-HCC group in Glb， AST， and GGT （all P<0.05）. The HBV-HCC group had significantly higher serum levels of CDK1 and AURKA than the HBV-LC group， the CHB group， and the control group （all P<0.05）. There was a significant positive correlation between CDK1 and AURKA in the overall study population and the HBV-HCC patients （r=0.526 6 and 0.815 2， P<0.001）. With the control group as reference， CDK1 had an AUC of 0.832 3 in the diagnosis of HBV-HCC， with a sensitivity of 92.86% and a specificity of 75%， and AURKA had an AUC of 0.886 6 in the diagnosis of HCC， with a sensitivity of 95.80% and a specificity of 74%. With the CHB group as reference， CDK1 had an AUC of 0.833 3 in the diagnosis of HBV-HCC， with a sensitivity of 93.75% and a specificity of 75%， and AURKA had an AUC of 0.972 7 in the diagnosis of HBV-HCC， with a sensitivity of 95.83% and a specificity of 91.67%. With the HBV-LC group as reference， CDK1 had an AUC of 0.608 5 in the diagnosis of HBV-HCC， with a sensitivity of 66.67% and a specificity of 54.17%， and AURKA had an AUC of 0.762 2 in the diagnosis of HBV-HCC， with a sensitivity of 95.83% and a specificity of 47.92%. Conclusion The serum levels of CDK1 and AURKA increase with the progression of hepatitis B-associated chronic liver disease， and significant increases in serum CDK1 and AURKA have a certain value in the diagnosis of HBV-HCC.
- Carcinoma， Hepatocellular /
- Cyclin-Dependent Kinases /
- Aurora Kinase A

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图 1 各组血清中CDK1和AURKA水平

Figure 1. Serum levels of CDK1 and AURKA in each group

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图 2 血清中CDK1与AURKA水平的相关性

注： a，总纳入人群；b，HBV-HCC患者。

Figure 2. Correlation between serum CDK1 and AURKA levels

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图 3 CDK1和AURKA诊断HBV相关HCC的ROC曲线

注： a，对照组 vs HBV-HCC组；b，CHB组vs HBV-HCC组；c， HBV-LC组 vs HBV-HCC组。

Figure 3. ROC curve of CDK1 and AURKA in diagnosis of HBV-HCC

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表 1 患者基本资料的比较

Table 1. Comparison of basic data of patients

组别	例数	男/女（例）	年龄（岁）
对照组	50	28/22	53.09±5.43
HBV-HCC组	50	34/16	56.04±2.70
HBV-LC组	50	28/22	55.83±3.58
CHB组	50	36/14	54.71±3.12
统计值		χ²=7.72	F=3.11
P值		0.52	0.07

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表 2 各组肝功能指标的比较

Table 2. Comparison of liver function indexes in each group

指标	对照组（n=50）	HBV-HCC组（n=50）	HBV-LC组（n=50）	CHB组（n=50）	统计值	P值
TP（g/L）	72.76±4.56	66.94±8.26^1）	68.68±8.20	70.57±9.02	F=3.25	0.024
Alb（g/L）	44.04±3.12	35.03±5.78^1）	33.64±6.24	40.68±5.56^2）	F=25.30	<0.001
Glb（g/L）	28.72±3.10	31.93±4.86^1）	36.92±7.56^2）	27.99±4.75^2）	F=21.17	<0.001
TBil（µmoL/L）	16.30（12.10～19.40）	28.27（19.12～46.54）^1）	32.90（21.33～51.30）	26.14（15.50～36.28）	H=20.58	<0.001
DBil（µmoL/L）	4.30（3.30～5.00）	9.30（5.81～21.85）^1）	10.98（5.90～18.45）	4.61（3.40～9.70）^2）	H=35.64	<0.001
IBil（µmoL/L）	11.50（8.10～13.30）	17.10（11.80～23.26）^1）	18.60（15.20～28.81）	14.22（11.57～30.38）	H=15.02	0.002
AST（U/L）	27.00（19.80～29.00）	54.50（38.00～81.71）^1）	35.00（24.00～35.00）^2）	22.16（16.00～34.00）^2）	H=39.28	<0.001
ALT（U/L）	19.00（12.00～30.00）	39.11（25.33～65.00）^1）	26.00（13.72～58.00）	25.00（13.00～70.00）	H=11.90	0.008
GGT（U/L）	18.20（15.40～55.60）	68.00（40.70～150.82）^1）	30.72（15.80～58.20）^2）	18.33（13.09～40.06）^2）	H=36.25	<0.001
ALP（U/L）	71.00（54.00～87.00）	103.84（86.40～232.95）^1）	81.00（58.00～114.00）	93.00（79.21～121.00）^2）	H=30.35	<0.001
注：TP，总蛋白；Glb，球蛋白。与对照组比较，1）P<0.05；与HBV-HCC组比较，2）P<0.05。

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表 3 CDK1及AURKA与肝功能各项指标的相关性（r_s ）

Table 3. Correlation between CDK1、AURKA and liver function indexe （r_s ）

指标	对照组		CHB组		HBV-LC组		HBV-HCC组
指标	CDK1	AURKA	CDK1	AURKA	CDK1	AURKA	CDK1	AURKA
TP	0.142	-0.249	-0.049	-0.058	0.009	-0.094	-0.314^2）	-0.247^1）
Alb	0.142	-0.079	-0.138	-0.133	-0.296^1）	-0.576^2）	-0.557^2）	-0.570^2）
Glb	0.215	-0.320	0.140	0.068	0.316^2）	0.485^2）	0.152	0.344^2）
TBil	0.054	0.250	0.221	0.158	0.167	0.387^2）	0.489^2）	0.338^2）
DBil	0.063	0.252	0.256^1）	0.188	0.229	0.478^2）	0.495^2）	0.406^2）
IBil	0.029	0.212	0.184	0.146	0.177	0.287^1）	0.420^2）	0.247^1）
ALT	0.001	0.045	0.273^1）	0.081	0.188	0.263^1）	0.334^2）	0.293^1）
AST	0.095	0.174	0.262^1）	0.038	0.198	0.368^2）	0.578^2）	0.478^2）
GGT	0.063	0.305	0.169	0.118	0.063	0.081	0.437^2）	0.380^2）
ALP	0.350	0.258	0.039	0.092	0.333^2）	0.345^2）	0.449^2）	0.443^2）
注：1）P<0.05；2）P<0.01。

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