人附睾蛋白4作为肾脏纤维化分子诊断标志物的临床价值

李红; 李耕; 刘星; 禹红

doi:10.16766/j.cnki.issn.1674-4152.003259

人附睾蛋白4作为肾脏纤维化分子诊断标志物的临床价值

doi: 10.16766/j.cnki.issn.1674-4152.003259

武汉市中医医院检验科，湖北武汉 430000

基金项目:

湖北省中医药管理局中医药科研项目 ZY2023F052

武汉市卫健委中医药科研项目 WZ22C69

详细信息

通讯作者:
禹红，E-mail：yuh_1969@163.com

中图分类号: R692R446
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- 被引次数: 0
出版历程
- 收稿日期: 2023-06-11
- 网络出版日期: 2024-01-13

Clinical value of HE4 as a molecular marker for renal fibrosis

Department of Clinical Laboratory, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430000, China

摘要

摘要: 目的探讨慢性肾脏病(CKD)患者血清人附睾蛋白4(HE4)的变化及其对肾脏纤维化的诊断价值。方法选取2020年1月-2022年1月于武汉市中医医院就诊的159例CKD患者, 分为CKD 1~5期组, 选择同期健康体检者39例为对照组。比较各组血清HE4、肌酐(Crea)、尿素氮(Bun)及尿液β2微球蛋白(β2-M)水平。采用受试者工作特征(ROC)曲线评价HE4辅助诊断CKD的价值, 并通过GEO数据库分析HE4与肾脏纤维化的关系。结果 CKD 1~5期患者血清HE4水平分别为(84.36±7.53) pmol/L、(148.90±16.46) pmol/L、(259.80±36.93) pmol/L、(438.80±81.92) pmol/L、(1 002.34±68.55) pmol/L, 均高于对照组[(33.80±1.99) pmol/L, 均P < 0.05];且随着CKD的进展, 患者血清HE4逐渐升高。血清HE4、Crea、Bun及尿液β2-M预测CKD的曲线下面积分别为0.998、0.801、0.748、0.826, HE4对CKD辅助诊断的敏感性和特异性分别为0.983和0.949。GEO数据库分析发现, HE4基因WFDC2与肾脏纤维化密切相关, 不同疾病诱导的肾脏纤维化模型中的WFDC2基因表达均明显升高(均P < 0.05)。结论血清HE4水平升高与肾脏纤维化相关, 对肾脏纤维化导致的慢性肾功能不全具有较高的临床价值。
- 人附睾蛋白4 /
- 慢性肾脏疾病 /
- 肾脏纤维化 /
- 标志物
Abstract: Objective To investigate the changes of serum human epididymis protein 4(HE4) in patients with chronic kidney disease (CKD) and its diagnostic value for renal fibrosis. Methods A total of 159 patients with CKD who were treated in Wuhan Hospital of Traditional Chinese Medicine from January 2020 to January 2022 were selected and divided into CKD 1-5 stage groups, and 39 healthy subjects were selected as the control group.The levels of serum HE4, creatinine (Crea), blood urea nitrogen (Bun) and urine β2-microglobulin (β2-M) in each group were compared.The receiver operating characteristic (ROC) curve was used to evaluate the value of HE4 in the auxiliary diagnosis of CKD.The relationship between HE4 and renal fibrosis was analyzed by GEO database. Results Serum HE4 levels in CKD 1-5 stage patients were (84.36±7.53) pmol/L, (148.90±16.46) pmol/L, (259.80±36.93) pmol/L, (438.80±81.92) pmol/L, and (1 002.34±68.55) pmol/L, respectively, were all higher than that of control group[(33.80±1.99) pmol/L, all P < 0.05].With the progression of CKD, serum HE4 increased gradually.The areas under the curve of serum HE4, Crea, Bun and urine β2-M for predicting CKD were 0.998, 0.801, 0.748 and 0.826, respectively (all P < 0.05).The sensitivity and specificity of HE4 for the diagnosis of CKD were 0.983 and 0.949, respectively.GEO database analysis showed that HE4 gene WFDC2 was closely related to renal fibrosis, and WFDC2 gene expression was significantly increased in renal fibrosis models induced by different diseases (all P < 0.05). Conclusion Elevated serum HE4 level is associated with renal fibrosis and has a high clinical value for chronic renal insufficiency caused by renal fibrosis.
- Human epididymis protein 4 /
- Chronic kidney disease /
- Renal fibrosis /
- Biomarker

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图 1 血清HE4、Crea、BUN及尿液β2-M辅助诊断CKD的ROC曲线

Figure 1. ROC curves of serum HE4, Crea, BUN and urinary β2-M in the adjuvant diagnosis of CKD

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图 2 HIV诱导的肾脏纤维化细胞模型中WFDC2基因的表达量

Figure 2. Expression of WFDC2 gene in an HIV-induced renal fibrosis cell model

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图 3 高血压相关钙调控基因过表达诱导的肾脏细胞纤维化中WFDC2基因的表达量

Figure 3. Expression of WFDC2 gene in renal cell fibrosis induced by overexpression of hypertension-related calcium regulatory gene

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表 1 各CKD组与对照组血清HE4、Crea、BUN、尿β2-M水平比较(x±s)

Table 1. Comparison of Serum HE4, Crea, BUN and urinary β2-M levels between CKD group and control group (x±s)

组别	例数	HE4 (pmol/L)	Crea (μmol/L)	BUN (mmol/L)	尿β2-M (mg/L)
对照组	39	33.80±1.99	59.23±2.23	4.69±0.17	0.17±0.03
CKD 1期组	41	84.36±7.53^a	56.10±1.19	4.55±0.23	0.69±0.18
CKD 2期组	22	148.90±16.46^ab	80.01±1.83^a	7.39±0.76^a	1.11±0.33^a
CKD 3期组	32	259.80±36.93^abc	132.50±11.70^a	9.58±1.94^a	1.11±0.21^a
CKD 4期组	27	438.80±81.92^abcd	219.70±9.42^a	12.60±1.31^a	2.47±0.38^a
CKD 5期组	37	1 002.34±68.55^abcde	607.80±41.88^a	21.47±1.79^a	2.79±0.31^a
F值		2 321.310	4 523.000	989.410	585.000
P值		< 0.001	< 0.001	< 0.001	< 0.001
注：与对照组比较，^aP < 0.001；与CKD 1期组比较，^bP < 0.05；与CKD 2期组比较，^cP < 0.05；与CKD 3期组比较，^dP < 0.05；与CKD 4期组比较，^eP < 0.05。

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表 2 血清HE4、Crea、BUN及尿液β2-M对CKD的诊断效能

Table 2. Diagnostic efficacy of serum HE4, Crea, BUN and urinary β2-M in CKD

项目	AUC	Cut-off	特异度	灵敏度	95% CI
HE4	0.998	44.7	0.949	0.983	0.972~1.000
Crea	0.801	80.5	0.974	0.619	0.733~0.868
BUN	0.748	6.51	0.974	0.568	0.675~0.821
β2-M	0.826	0.28	0.974	0.737	0.764~0.889

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