WDR5和miR-455-5p表达在宫颈癌诊断和预后评估中的价值

doi:10.3969/j.issn.1673-8640.2025.09.007

摘要/Abstract

摘要：

目的探讨WD重复序列蛋白5（WDR5）和miR-455-5p在宫颈癌诊断和预后评估中的价值。方法选取2018年9月—2020年6月保定市第二中心医院宫颈癌患者78例（宫颈癌组）和宫颈上皮内瘤变（CIN）（Ⅱ~Ⅲ级）患者78例（CIN组），以78名健康体检女性作为正常对照组。收集所有研究对象的临床资料，并检测血清WDR5蛋白水平和WDR5 mRNA、miR-455-5p相对表达量，同时检测宫颈癌患者癌组织和癌旁组织（距肿瘤边缘>5 cm）WDR5蛋白的表达情况。对宫颈癌患者随访3年。采用Pearson相关分析评估血清WDR5 mRNA与miR-455-5p表达的相关性。采用Kaplan-Meier生存曲线分析WDR5 mRNA、miR-455-5p表达与宫颈癌患者预后（死亡）的关系。采用Cox回归分析评估宫颈癌患者预后的影响因素。采用受试者工作特征（ROC）曲线评价血清WDR5 mRNA、miR-455-5p诊断宫颈癌和判断宫颈癌患者预后（死亡）的效能。结果宫颈癌组、CIN组和正常对照组血清WDR5 mRNA相对表达量和WDR5水平均依次升高（P<0.001），血清miR-455-5p相对表达量依次降低（P<0.001）。宫颈癌患者癌组织WDR5阳性率（76.92%）高于癌旁组织（11.54%）（P<0.001）。不同TNM分期、肿瘤最大直径、浸润深度、分化程度和有无淋巴转移的宫颈癌患者之间血清WDR5 mRNA、miR-455-5p相对表达量差异均有统计学意义（P<0.05）。宫颈癌患者血清WDR5 mRNA与miR-455-5p呈负相关（r=-0.405，P<0.001）。血清WDR5 mRNA、miR-455-5p单项检测和联合检测诊断宫颈癌的AUC分别为0.767、0.756、0.883，判断宫颈癌患者预后的曲线下面积（AUC）分别为0.857、0.798、0.861。WDR5高表达组3年总生存率低于WDR5低表达组（Log-rank χ²=5.932，P=0.015），miR-455-5p高表达组3年总生存率高于miR-455-5p低表达组（Log-rank χ²=4.859，P=0.027）。WDR5 mRNA高表达、miR-455-5p低表达、中低分化、TNM分期Ⅲ~Ⅳ期、浸润深度≥1/2肌层、肿瘤最大直径≥4 cm、有淋巴转移均是宫颈癌患者死亡的危险因素（P<0.05）。结论宫颈癌患者血清WDR5水平和WDR5 mRNA表达均升高，miR-455-5p表达降低，且均与临床病理特征密切相关，或可作为宫颈癌患者诊断、病情监测和预后评估的生物标志物。

关键词: WD重复序列蛋白5, miR-455-5p, 宫颈癌, 临床病理特征, 预后评估

Abstract:

Objective To investigate the roles of WD repeat-containing protein 5（WDR5） and miR-455-5p in the diagnosis and prognosis assessment of cervical cancer. Methods A total of 78 patients with cervical cancer（cervical cancer group） and 78 patients with cervical intraepithelial neoplasia（CIN）（grade Ⅱ-Ⅲ）（CIN group） from September 2018 to June 2020 in Baoding Second Central Hospital were enrolled，and 78 healthy females undergoing physical examination were enrolled as healthy control group. The clinical data were collected，and the levels of serum WDR5 protein and the relative expression levels of WDR5 mRNA and miR-455-5p were determined. The expression of WDR5 protein in cancer tissues and adjacent tissues（>5 cm away from the tumor margin） was also determined. The cervical cancer patients were followed up for 3 years. Pearson correlation analysis was used to evaluate the correlation between serum WDR5 mRNA and miR-455-5p expression. Kaplan-Meier survival curve was used to analyze the relationship between the expression of WDR5 mRNA and miR-455-5p and the prognosis（death）of cervical cancer patients. Cox regression analysis was used to evaluate the influencing factors of prognosis in cervical cancer patients. Receiver operating characteristic（ROC）curves were used to evaluate the efficacy of serum WDR5 mRNA and miR-455-5p in diagnosing cervical cancer and predicting the prognosis（death）of cervical cancer patients. Results The relative expression levels of WDR5 mRNA and the levels of WDR5 in serum were successively increased in cervical cancer group，CIN group and healthy control group（P<0.001），while the relative expression levels of miR-455-5p were successively decreased（P<0.001）. The positive rate of WDR5 in cancer tissues of cervical cancer patients（76.92%） was higher than that in adjacent tissues（11.54%）（P<0.001）. There was statistical significance in the relative expression levels of serum WDR5 mRNA and miR-455-5p among cervical cancer patients with different TNM stages，maximum tumor diameters，invasion depths，differentiation degrees and lymphatic metastasis（P<0.05）. Serum WDR5 mRNA was negatively correlated with miR-455-5p in cervical cancer patients（r=-0.405，P<0.001）. The areas under curves（AUC）of single and combined determinations of serum WDR5 mRNA and miR-455-5p for diagnosing cervical cancer were 0.767，0.756 and 0.883，respectively. The AUC for predicting the prognosis（death）of cervical cancer patients were 0.857，0.798 and 0.861. The 3-year overall survival rate of high-expression group of WDR5 was lower than that of low-expression group（Log-rank χ²=5.932，P=0.015），and the 3-year overall survival rate of high-expression group of miR-455-5p was higher than that of low-expression group（Log-rank χ²=4.859，P=0.027）. High expression of WDR5 mRNA，low expression of miR-455-5p，moderate to low differentiation，TNM stage Ⅲ-Ⅳ，invasion depth≥1/2 of the myometrium，maximum tumor diameter≥4 cm and lymphatic metastasis were all risk factors for death in patients with cervical cancer（P<0.05）. Conclusions The levels of WDR5 in serum and the expression of WDR5 mRNA in patients with cervical cancer are increased，while the expression of miR-455-5p is decreased，and these are related to the clinical pathological characteristics. They may serve as biomarkers for the diagnosis，disease monitoring and prognosis assessment of patients with cervical cancer.

Key words: WD repeat-containing protein 5, MicroRNA-455-5p, Cervical cancer, Clinical pathological characteristic, Prognosis evaluation

中图分类号:

R446.1

刘昊, 付淼, 刘蓬, 田文, 王莎, 尹晓梅, 王东海. WDR5和miR-455-5p表达在宫颈癌诊断和预后评估中的价值[J]. 检验医学, 2025, 40(9): 867-874.

LIU Hao, FU Miao, LIU Peng, TIAN Wen, WANG Sha, YIN Xiaomei, WANG Donghai. Expressions and roles of WDR5 and miR-455-5p in cervical cancer patients[J]. Laboratory Medicine, 2025, 40(9): 867-874.

图/表 14

参考文献 16

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项目	上游引物（5'~3'）	下游引物（5'~3'）
WDR5 mRNA	GTGTGAGGATATGGGACGTGA	GAACGGCTGAGACTGGGTC
GAPDH	GAGTCAACGGATTTGGTCGT	GACAAGATTCCCGTTCTCAG
miR-455-5p	GCCGTATGTGCCTTTGGACT	GTGCAGGGTCCGAGGT
U6	CTCGCTTCGGCAGCACA	AACGCTTCACGAATTTGCGT

项目	上游引物（5'~3'）	下游引物（5'~3'）
WDR5 mRNA	GTGTGAGGATATGGGACGTGA	GAACGGCTGAGACTGGGTC
GAPDH	GAGTCAACGGATTTGGTCGT	GACAAGATTCCCGTTCTCAG
miR-455-5p	GCCGTATGTGCCTTTGGACT	GTGCAGGGTCCGAGGT
U6	CTCGCTTCGGCAGCACA	AACGCTTCACGAATTTGCGT

组别	例数	年龄/岁	BMI/（kg·m^-2）	产次/次
宫颈癌组	78	44.51±7.59	23.11±4.17	1.72±0.61
CIN组	78	44.13±7.61	23.71±4.14	1.64±0.53
正常对照组	78	43.58±7.24	23.84±4.09	1.75±0.59
F值		0.305	0.692	0.756
P值		0.738	0.501	0.471

组别	例数	年龄/岁	BMI/（kg·m^-2）	产次/次
宫颈癌组	78	44.51±7.59	23.11±4.17	1.72±0.61
CIN组	78	44.13±7.61	23.71±4.14	1.64±0.53
正常对照组	78	43.58±7.24	23.84±4.09	1.75±0.59
F值		0.305	0.692	0.756
P值		0.738	0.501	0.471

组别	例数	WDR5 mRNA	WDR5蛋白/（pg·mL^-1）	miR-455-5p
宫颈癌组	78	1.61±0.43^*#	36.62±4.29^*#	0.75±0.21^*#
CIN组	78	1.29±0.21^*	32.98±3.95^*	0.91±0.18^*
正常对照组	78	1.00±0.29	18.34±2.18	1.01±0.27
F值		69.580	565.230	26.940
P值		<0.001	<0.001	<0.001