HAX1、GINS2高表达和TLR4低表达与子宫内膜癌不良预后的关联研究OA

Objective To investigate the expression changes of hematopoietic cell-specific pro-tein 1 associated with X-linked inhibitor of apoptosis protein(HAX1),GINS complex subunit 2(GINS2),and Toll-like receptor 4(TLR4)in endometrial cancer(EC)tissues and their association with the prognosis of EC patients.Methods Cancer tissues(study group)and adjacent normal en-dometrial tissues(control group,≥5 cm from the edge of the cancer tissue and confirmed by patholo-gy to be free of tumor infiltration)from 90 EC patients admitted to Wuhan Hospital of Traditional Chi-nese Medicine and Hubei Cancer Hospital from January 2019 to November 2020 were retrospectively collected.Immunohistochemistry was used to detect the expression levels of HAX1,GINS2,and TLR4 in samples of the two groups.Patients were followed up for 5 years.The prognoses of patients with different protein expression levels of HAX1,GINS2,and TLR4 were compared,and multivariate Cox regression analysis was used to screen for influencing factors of EC prognosis.Results The positive expression rates of HAX1 and GINS2 proteins in the study group were 62.22％and 82.22％,respectively,which were higher than those in the control group(24.44％and 46.67％,respectively).The positive expression rate of TLR4 protein in the study group was 27.78％,which was lower than 75.56％in the control group,and the differences were statistically significant(P＜0.001).There was a statistically significant difference in the positive expression rate of GINS2 pro-tein among patients of different ages(P=0.027).There were statistically significant differences in the positive expression rates of HAX1,GINS2,and TLR4 proteins among patients with different In-ternational Federation of Gynecology and Obstetrics(FIGO)stages and different lymph node metas-tasis statuses(P＜0.05).There were statistically significant differences in the positive expression rate of HAX1 protein among patients with different depths of myometrial invasion and degrees of cell differentiation(P＜0.001).Spearman rank correlation analysis showed that HAX1 protein expres-sion was positively correlated with GINS2 protein expression(r=0.521,P＜0.001),HAX1 pro-tein expression was negatively correlated with TLR4 protein expression(r=-0.437,P＜0.001),and GINS2 protein expression was negatively correlated with TLR4 protein expression(r=-0.485,P＜0.001).The 5-year survival rate of patients with negative HAX1 protein expression was higher than that of patients with positive expression,the 5-year survival rate of patients with negative GINS2 protein expression was higher than that of patients with positive expression,and the 5-year survival rate of patients with positive TLR4 protein expression was higher than that of patients with negative expression,with statistically significant differences(P＜0.05).Multivariate Cox regression analysis showed that FIGO stage Ⅲ-Ⅳ,lymph node metastasis,menopausal status,low cell differentiation degree,myometrial invasion depth≥1/2 of the myometrium,high expression of HAX1,high ex-pression of GINS2,and low expression of TLR4 were independent risk factors for the prognosis of EC patients(P＜0.05).Conclusion The expressions of HAX1 and GINS2 are increased,and the ex-pression of TLR4 is decreased in endometrial cancer tissues.These three factors,along with FIGO stage Ⅲ-Ⅳ,lymph node metastasis,menopausal status,low cell differentiation degree,and myo-metrial invasion depth≥1/2 of the myometrium,are all independent risk factors for the prognosis of EC patients.