血清CD46、KLF7、FURIN与慢性宫颈炎合并HPV感染患者临床病理特征的关系及预后预测价值

张志英; 时培景

血清CD46、KLF7、FURIN与慢性宫颈炎合并HPV感染患者临床病理特征的关系及预后预测价值

张志英¹,
时培景^2, ,

1.
烟台山医院健康体检科，山东烟台　264000
2.
济南市第三人民医院妇科，山东济南　250132

基金项目: 山东省医药卫生科技发展计划项目2023WS097

详细信息

作者简介:
张志英（1974～），女，江西上饶人，医学学士，副主任医师，主要从事妇女保健研究工作

通讯作者:
时培景，E-mail：spj197912@163.com

中图分类号: R711.32
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出版历程
- 收稿日期: 2025-10-23

Relationship Between Serum CD46，KLF7，FURIN and Clinicopathological Features in Patients with Chronic Cervicitis Combined with HPV Infection and Their Prognostic Predictive Value

Zhiying ZHANG¹,
Peijing SHI^{2
, ,}

1.
Department of Health Examination，Yantai Mountain Hospital，Yantai Shandong 264000
2.
Department of Gynecology，The Third People’s Hospital of Jinan ，Jinan Shandong 250132，China

摘要

摘要: 目的探讨血清膜辅因子蛋白（membrane cofactor protein，CD46）、Krüppel样因子7（krüppel-like factor 7，KLF7）、弗林蛋白酶（Furin，FURIN）与慢性宫颈炎合并HPV感染患者临床病理特征的关系及预后预测价值。方法选取2022年12月至2024年12月烟台山医院收治的217例确诊HPV感染的慢性宫颈炎患者、217例单纯慢性宫颈炎患者及217例妇科体检健康的志愿者为研究对象，分别纳入宫颈炎合并HPV组、单纯宫颈炎组、健康组。根据治疗3个月后预后疗效评估，将慢性宫颈炎合并HPV患者分为疗效显著组（n = 133）和疗效不佳组（n = 84）。采用ELISA法检测血清CD46、KLF7、FURIN水平；采用Spearman法和Pearson法分析CD46、KLF7、FURIN水平与HPV危险度及炎症因子的相关性；采用 Cox回归筛选宫颈炎合并HPV患者疗效不佳的影响因素；采用ROC曲线分析CD46、KLF7、FURIN水平预测宫颈炎合并HPV患者疗效不佳的价值；比较不同CD46、KLF7、FURIN截断值水平宫颈炎合并HPV患者发生疗效不佳的相对危险度。结果宫颈炎合并HPV组患者血清CD46、KLF7、FURIN水平较单纯宫颈炎组、健康组依次升高（P < 0.05）。宫颈炎合并 HPV 组患者血清 CD46、KLF7、FURIN 水平显著高于单纯宫颈炎组和健康组（P < 0.05），单纯宫颈炎组高于健康组（P < 0.05）。HPV高危型组患者血清 CD46、KLF7、FURIN 水平显著高于中危型组和低危型组（P < 0.05），中危型组高于低危型组（P < 0.05）。宫颈炎合并HPV组炎症因子IL-10、TNF-α水平高于单纯宫颈炎组患者（P < 0.05），IFN-γ水平低于单纯宫颈炎组（P < 0.05）。Spearman 相关分析显示，CD46、KLF7、FURIN 水平与 HPV 危险度呈正相关（r_s = 0.523、0.486、0.507，P < 0.05）；Pearson 相关分析显示，CD46、KLF7、FURIN 水平与 IL-10、TNF-α 呈正相关（r = 0.492、0.535、0.527，P < 0.05），与 IFN-γ 呈负相关（r = −0.538、−0.511、−0.479，P < 0.05）。宫颈炎合并HPV疗效不佳组患者血清CD46、KLF7、FURIN水平显著高于疗效显著组患者（P < 0.05）；两组年龄、BMI比较，差异无统计学意义（P > 0.05）。单因素 Cox 比例风险回归分析显示，年龄、BMI均与宫颈炎合并 HPV 患者疗效不佳无关（P > 0.05）。将上述有意义的纳入多因素Cox回归发现，CD46、KLF7、FURIN水平升高等均为宫颈炎合并HPV患者疗效不佳的影响因素（P < 0.05）。CD46、KLF7、FURIN联合预测宫颈炎合并HPV患者疗效不佳的AUC为0.947（95%CI：0.918～0.975），优于CD46（Z = 2.862，P < 0.05）、KLF7（Z = 3.584，P < 0.05）、FURIN（Z = 3.116，P < 0.05）单一预测的AUC。CD46≥253.39、KLF7≥5.91、FURIN≥135.41表达的宫颈炎合并HPV患者预后疗效不佳的相对危险度是CD46 < 253.39、KLF7 < 5.91、FURIN < 135.41患者的1.958、1.691和2.041倍（χ² = 34.775、22.380、40.412，P < 0.05）。结论慢性宫颈炎合并HPV感染患者血清CD46、KLF7、FURIN水平升高，三者与HPV危险度及炎症因子水平存在相关性，CD46、KLF7、FURIN联合预测宫颈炎合并HPV患者疗效不佳的较高。
- CD46 /
- KLF7 /
- FURIN /
- 慢性宫颈炎合并HPV感染 /
- 临床病理特征 /
- 预后 /
- 预测
Abstract: Objective To investigate the relationship between serum membrane cofactor protein （CD46）, Krüppel-like factor 7 （KLF7）, Furin protease （FURIN） and clinical-pathological characteristics of chronic cervicitis combined with HPV infection, and their predictive value for prognosis. Methods A total of 217 patients diagnosed with chronic cervicitis complicated by HPV infection, 217 patients with chronic cervicitis, and 217 healthy volunteers from gynecological examination admitted to Yantai Mountain Hospital between December 2022 and December 2024 were enrolled in this study and divided into chronic cervicitis with HPV group, chronic cervicitis group, and healthy control group, respectively. Based on evaluation of therapeutic efficacy after three months of treatment, patients in the chronic cervicitis with HPV group were divided into significant efficacy group （n = 133） and poor efficacy group （n = 84）. Serum levels of CD46, KLF7, and FURIN were measured using ELISA. Spearman and Pearson correlation analyses were employed to assess the correlation between these biomarker levels, HPV risk stratification, and inflammatory cytokine levels. Cox regression analysis was employed to screen for factors affecting poor efficacy in cervicitis complicated with HPV patients. ROC curve analysis was used to evaluate the value of CD46, KLF7, and FURIN levels in predicting poor efficacy in cervicitis combined with HPV patients. Relative risks of poor efficacy at different cutoff values of CD46, KLF7, and FURIN were compared. Results Serum levels of CD46, KLF7, and FURIN in the cervicitis complicated with HPV group were progressively elevated compared to the cervicitis group and healthy control group （P < 0.05）. Serum CD46, KLF7, and FURIN levels in the cervicitis combined with HPV group were significantly higher than those in the cervicitis group and healthy control group （P < 0.05）, and the cervicitis group was higher than the healthy control group （P < 0.05）. Serum CD46, KLF7, and FURIN levels in the high-risk HPV type group were significantly higher than those in the intermediate-risk and low-risk type groups （P < 0.05）, and the intermediate-risk group was higher than the low-risk group （P < 0.05）. Inflammatory factors IL-10 and TNF-α levels in the cervicitis combined with HPV group were higher than those in the cervicitis group （P < 0.05）, while IFN-γ levels were lower （P < 0.05）. Spearman correlation analysis showed that CD46, KLF7, and FURIN levels were positively correlated with HPV risk stratification （r_s = 0.523, 0.486, 0.507, P < 0.05）. Pearson correlation analysis demonstrated that CD46, KLF7, and FURIN levels were positively correlated with IL-10 and TNF-α （r = 0.492, 0.535, 0.527, P < 0.05） and negatively correlated with IFN-γ （r = −0.538, −0.511, −0.479, P < 0.05）. Serum CD46, KLF7, and FURIN levels in the poor efficacy group were significantly higher than those in the significant efficacy group （P < 0.05）; there was no statistically significant difference in age and BMI between the two groups （P > 0.05）. Univariate Cox proportional hazards regression analysis showed that neither age nor BMI was associated with poor efficacy in cervicitis combined with HPV patients （P > 0.05）. Multivariate Cox regression analysis including significant variables revealed that elevated CD46, KLF7, and FURIN levels were all independent factors affecting poor efficacy in cervicitis combined with HPV patients （P < 0.05）. The combined AUC of CD46, KLF7, and FURIN for predicting poor efficacy in cervicitis combined with HPV patients was 0.947 （95%CI: 0.918～0.975）, which was superior to the individual AUC values of CD46 （Z = 2.862, P < 0.05）, KLF7 （Z = 3.584, P < 0.05）, and FURIN （Z = 3.116, P < 0.05）. The relative risk of poor prognosis in cervicitis combined with HPV patients with CD46≥253.39, KLF7≥5.91, and FURIN≥135.41 expression was 1.958, 1.691, and 2.041 times that of patients with CD46 < 253.39, KLF7 < 5.91, and FURIN < 135.41, respectively （χ² = 34.775, 22.380, 40.412, P < 0.05）. Conclusion Serum CD46, KLF7, and FURIN levels are elevated in patients with chronic cervicitis combined with HPV infection, and all three are correlated with HPV risk stratification and inflammatory factor levels. The combined detection of CD46, KLF7, and FURIN has high predictive value for poor efficacy in cervicitis combined with HPV patients.
- CD46 /
- KLF7 /
- FURIN /
- Chronic cervicitis complicated with HPV infection /
- Clinical pathological features /
- Prognosis /
- Prediction

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图 1 CD46、KLF7、FURIN水平预测宫颈炎合并HPV患者疗效不佳的ROC曲线

Figure 1. ROC curves of CD46，KLF7，and FURIN levels for predicting poor therapeutic effect in patients with cervical inflammation complicated with HPV

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表 1 宫颈炎合并HPV组、单纯宫颈炎组、健康组一般资料比较[（$ \bar x \pm s $）/n（%）]

Table 1. Comparison of general data among cervical inflammation combined with HPV group，cervical inflammation group and healthy group[（$ \bar x \pm s $）/n（%）]

指标	宫颈炎合并HPV组（n = 217）	单纯宫颈炎组（n = 217）	健康组（n = 217）	F/t/χ²	P
年龄（岁）	52.56 ± 8.42	51.38 ± 8.34	51.75 ± 8.53	1.112	0.329
BMI（kg/m²）	23.84 ± 2.37	24.15 ± 2.28	23.76 ± 2.41	1.662	0.191
孕次（次）	2.23 ± 0.35	2.21 ± 0.29	2.20 ± 0.26	0.554	0.575
产次（次）	2.14 ± 0.19	2.11 ± 0.20	2.06 ± 0.18	1.400	0.247
宫颈长度（cm）	4.24 ± 0.71	4.21 ± 0.70	4.23 ± 0.72	0.100	0.904
性生活频率（次/周）				4.167	0.125
< 3	84（38.71）	93（42.86）	105（48.39）
≥3	133（61.29）	124（57.14）	112（51.61）
肠道菌群				5.210	0.157
衣原体	34（15.67）	46（21.20）
霉菌	42（19.35）	51（23.50）
支原体	85（39.17）	79（36.41）
其它	56（25.81）	41（18.89）

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表 2 宫颈炎合并HPV组、单纯宫颈炎组、健康组血清CD46、KLF7、FURIN水平比较（$ \bar x \pm s $）

Table 2. Comparison of serum CD46，KLF7，and FURIN levels among cervical inflammation with HPV group，cervical inflammation group，and healthy group（$ \bar x \pm s $）

组别	n	CD46（pg/mL）	KLF7（ng/mL）	FURIN（IU/L）
健康组	217	105.69 ± 21.36	3.45 ± 0.84	64.25 ± 17.56
单纯宫颈炎组	217	163.48 ± 39.57^a	4.81 ± 1.06^a	87.49 ± 21.35^a
宫颈炎合并HPV组	217	244.51 ± 42.36^ab	6.19 ± 1.34^ab	125.36 ± 29.54^ab
F		520.698	337.090	378.418
P		< 0.001^*	< 0.001^*	< 0.001^*
^*P < 0.05；与健康组比较，^aP < 0.05；与单纯宫颈炎组比较，^bP < 0.05。

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表 3 不同危险型HPV患者血清CD46、KLF7、FURIN水平比较（$ \bar x \pm s $）

Table 3. Comparison of serum CD46，KLF7，and FURIN levels in patients with different high-risk HPV types（$ \bar x \pm s $）

组别	n	CD46（pg/mL）	KLF7（ng/mL）	FURIN（IU/L）
HPV低危型组	98	215.36 ± 35.42	5.12 ± 1.12	104.54 ± 23.45
HPV中危型组	37	248.49 ± 41.67^a	6.04 ± 1.43^a	128.68 ± 28.64^a
HPV高危型组	82	277.27 ± 49.24^ab	7.54 ± 1.58^ab	148.75 ± 33.29^ab
F		48.317	70.654	54.387
P		< 0.001^*	< 0.001^*	< 0.001^*
^*P < 0.05；与HPV低危组比较，^aP < 0.05；与HPV中危组比较，^bP < 0.05。

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表 4 宫颈炎合并HPV组和单纯宫颈炎组炎症因子水平比较（$ \bar x \pm s $）

Table 4. Comparison of inflammatory factor levels between the cervicitis combined with HPV group and cervicitis group（$ \bar x \pm s $）

组别	n	IFN-γ（pg/mL）	IL-10（µg/L）	TNF-α（µg/L）
单纯宫颈炎组	217	16.28 ± 4.34	13.64 ± 3.76	11.56 ± 2.84
宫颈炎合并HPV组	217	9.57 ± 2.64	19.52 ± 4.57	15.37 ± 4.11
t		19.458	14.636	11.234
P		< 0.001^*	< 0.001^*	< 0.001^*
^*P < 0.05。

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表 5 CD46、KLF7、FURIN水平与HPV危险度及炎症因子的相关性

Table 5. Correlation between CD46，KLF7，FURIN levels and HPV risk and inflammatory factors

指标	CD46		KLF7		FURIN
指标	r/r_s	P	r/r_s	P	r/r_s	P
HPV危险度	0.523	0.015^*	0.486	0.033^*	0.507	0.023^*
IFN-γ	−0.538	0.001^*	−0.511	0.019^*	−0.479	0.030^*
IL-10	0.492	0.031^*	0.535	0.007^*	0.527	0.011^*
TNF-α	0.504	0.026^*	0.520	0.018^*	0.513	0.020^*
^*P < 0.05。

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表 6 疗效显著组和疗效不佳组患者年龄、BMI、血清CD46、KLF7、FURIN水平比较（$ \bar x \pm s $）

Table 6. Comparison of age，BMI，serum CD46，KLF7，and FURIN levels between the patients in the highly effective group and the ineffective group（$ \bar x \pm s $）

组别	n	年龄（岁）	BMI（kg/m²）	CD46（pg/mL）	KLF7（ng/mL）	FURIN（IU/L）
疗效显著组	133	52.23 ± 8.15	23.61 ± 2.24	229.62 ± 39.54	5.84 ± 1.25	117.18 ± 28.54
疗效不佳组	84	52.48 ± 8.22	23.65 ± 2.41	268.09 ± 45.28	6.75 ± 1.49	138.32 ± 31.63
t		0.219	0.124	6.596	4.845	5.095
P		0.827	0.901	< 0.001^*	< 0.001^*	< 0.001^*
^*P < 0.05。

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表 7 宫颈炎合并HPV患者疗效不佳的单因素Cox比例风险回归分析

Table 7. Univariate Cox proportional hazards regression analysis for poor therapeutic outcomes in patients with cervicitis and HPV infection

影响因素	B	SE	Waldχ²	P	HR	95%CI
影响因素	B	SE	Waldχ²	P	HR	下限	上限
年龄	0.000	0.013	0.001	0.974	1.000	0.976	1.026
BMI	0.031	0.049	0.386	0.534	1.031	0.936	1.136
CD46	0.003	0.001	9.955	0.002^*	1.003	1.001	1.005
KLF7	0.247	0.086	8.374	0.004^*	1.281	1.083	1.514
FURIN	0.011	0.004	9.084	0.003^*	1.011	1.004	1.019
^*P < 0.05。

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表 8 宫颈炎合并HPV患者疗效不佳的Cox比例风险回归分析

Table 8. Cox proportional hazards regression analysis for poor therapeutic outcomes in patients with cervicitis and HPV infection

影响因素	B	SE	Waldχ²	P	HR	95%CI
影响因素	B	SE	Waldχ²	P	HR	下限	上限
CD46	0.002	0.001	4.853	0.028^*	1.002	1	1.004
KLF7	0.201	0.084	5.712	0.017^*	1.223	1.037	1.443
FURIN	0.009	0.004	5.625	0.018^*	1.009	1.002	1.017
^*P < 0.05。

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表 9 CD46、KLF7、FURIN水平预测宫颈炎合并HPV患者疗效不佳的价值

Table 9. The value of CD46，KLF7 and FURIN levels in predicting poor therapeutic effect in patients with cervical inflammation and HPV infection

项目	AUC	95%CI	敏感度（%）	特异性（%）	截断值	约登指数
CD46	0.865	0.816～0.914	82.10	71.40	253.39 pg/mL	0.535
KLF7	0.838	0.784～0.891	85.70	68.40	5.91 ng/mL	0.541
FURIN	0.855	0.804～0.905	81.00	75.90	135.41 IU/L	0.569
联合预测	0.947	0.918～0.975	91.70	82.70		0.744

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表 10 不同CD46、KLF7、FURIN水平对宫颈炎合并HPV患者疗效不佳的相对危险度

Table 10. Relative risk of poor therapeutic effect in patients with cervicitis complicated with HPV due to different levels of CD46，KLF7 and FURIN

指标	疗效显著组（n = 133）	疗效不佳组（n = 84）	相对危险度	χ²	P
指标	疗效显著组（n = 133）	疗效不佳组（n = 84）	（95%CI）	χ²	P
CD46
≥253.39	42	58	1.958（1.524～2.515）	29.090	< 0.001^*
< 253.39	91	26	1.958（1.524～2.515）	29.090	< 0.001^*
KLF7
≥5.91	40	52	1.691（1.339～2.135）	21.358	< 0.001^*
< 5.91	93	32	1.691（1.339～2.135）	21.358	< 0.001^*
FURIN
≥135.41	30	56	2.041（1.599～2.606）	41.870	< 0.001^*
< 135.41	103	28	2.041（1.599～2.606）	41.870	< 0.001^*
^*P < 0.05。

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血清CD46、KLF7、FURIN与慢性宫颈炎合并HPV感染患者临床病理特征的关系及预后预测价值

作者简介:
张志英（1974～），女，江西上饶人，医学学士，副主任医师，主要从事妇女保健研究工作

通讯作者:
时培景，E-mail：spj197912@163.com

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Relationship Between Serum CD46，KLF7，FURIN and Clinicopathological Features in Patients with Chronic Cervicitis Combined with HPV Infection and Their Prognostic Predictive Value

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[4]	顾海霞, 彭江丽, 陈安欣, 殷瑞, 肖琦琦, 陈洁. 维持性血液透析合并初治结核患者临床特点及预后分析, 昆明医科大学学报. 2025, 46(4): 129-135. doi: 10.12259/j.issn.2095-610X.S20250417
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[6]	贾世浩, 于克静, 张满鹤, 张福梅, 郝景察. 肠道代谢产物水平对急性胰腺炎患者心肌损伤及预后的预测价值, 昆明医科大学学报. 2025, 46(9): 137-144. doi: 10.12259/j.issn.2095-610X.S20250916
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血清CD46、KLF7、FURIN与慢性宫颈炎合并HPV感染患者临床病理特征的关系及预后预测价值

作者简介: 张志英（1974～），女，江西上饶人，医学学士，副主任医师，主要从事妇女保健研究工作

通讯作者: 时培景，E-mail：spj197912@163.com

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出版历程

Relationship Between Serum CD46，KLF7，FURIN and Clinicopathological Features in Patients with Chronic Cervicitis Combined with HPV Infection and Their Prognostic Predictive Value

计量

出版历程

目录

作者简介:
张志英（1974～），女，江西上饶人，医学学士，副主任医师，主要从事妇女保健研究工作

通讯作者:
时培景，E-mail：spj197912@163.com