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