Predictive value of tissue CDC25A and HMGB1 protein expression for long-term lymph node metastasis after hysterectomy in cervical cancer patients

XU Xiao-jing; WANG Yuan-hang; XU Yan

doi:10.13820/j.cnki.gdyx.20242934

Abstract：Objective To investigate the predictive value of tissue cell division cycle factor 25 A(CDC25A)and high mobility group box protein 1(HMGB1)expression for long-term lymph node metastasis in cervical cancer patients after hysterectomy.Methods A retrospective study was conducted on 350 cervical cancer patients who underwent hyster-ectomy at our hospital between January 2017 and December 2019.Patients were divided into metastasis(n=104)and non-metastasis(n=246)groups based on whether long-term lymph node metastasis occurred during the 3-year post-operative follow-up.Immunohistochemistry was used to detect the expression of CDC25A and HMGB1 in tumor tissues.Univariate and multivariate logistic regression analyses were performed to identify factors associated with long-term lymph node metastasis.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of CDC25A and HMGB1 expression,individually and in combination.Additionally,150 cervical cancer patients who under-went hysterectomy between January 2020 and June 2021 were selected as an external validation cohort in a 7∶3 training-to-validation ratio.Results Among the 350 patients in the training cohort,104(29.71％)experienced long-term lymph node metastasis.CDC25A and HMGB1 expression levels in tumor tissues were significantly associated with FIGO stage,deep muscle invasion,and differentiation degree(P＜0.05),but were not related to age,pathological type,or tumor size(P＞0.05).Multivariate logistic regression analysis identified low differentiation,FIGO stage Ⅰ B2+Ⅱ A2,deep muscle invasion(＞1/2),high CDC25A expression,and high HMGB1 expression as independent risk factors for long-term lymph node metastasis(P＜0.05).In the training cohort,the area under the curve(AUC)for predicting long-term lymph node metastasis using the combined detection of CDC25A and HMGB1 was 0.924(95％ CI:0.898-0.951),significantly higher than the AUCs for CDC25A(0.869,95％ CI:0.830-0.908)or HMGB1(0.859,95％CI:0.818-0.900)alone(Z=3.743,P＜0.001;Z=4.276,P＜0.001).Similarly,in the validation cohort,the combined AUC was 0.933(95％ CI:0.902-0.963),which was also significantly higher than the AUCs for CDC25A(0.866,95％ CI:0.820-0.912)or HMGB1(0.876,95％ CI:0.829-0.924)alone(Z=3.615,P＜0.001;Z=3.341,P=0.001).Conclusion High expression of CDC25A and HMGB1 is an independent risk factor for long-term lymph node metastasis in cervical cancer patients after hysterectomy.Their expression is associated with FIGO stage,deep muscle invasion,and differentiation degree.The combined detection of CDC25A and HMGB1 has high diagnostic value for predicting long-term lymph node metastasis in cervical cancer patients after hysterectomy.