关键词: 子宫内膜癌, 驱动蛋白家族成员11, 叉头框蛋白P3, 淋巴细胞活化基因-3, 预后

Abstract:

Objective To investigate the correlation between the expression levels of kinesin family member 11 （KIF11）， forkhead box protein P3 （FOXP3）， and lymphocyte activation gene-3 （LAG-3） in endometrial cancer tissues， and the clinicopathological characteristics as well as the long-term prognosis of patients. Methods Clinicopathological data and paraffin-embedded tissue specimens from 120 patients with endometrial cancer who were treated between January 2019 and December 2022 were retrospectively collected. Immunohistochemistry was employed to detect the expression of KIF11， FOXP3， and LAG-3 in cancer tissues， and these expressions were scored using the H-score method. Receiver operating characteristic （ROC） curves were plotted， with the lymph node metastasis status serving as the state variable， to analyze the diagnostic efficacy of each marker in differentiating lymph node metastasis. The optimal cut-off values were determined according to the Youden index to classify patients into high-expression and low-expression groups. The associations between the expression of the three markers and clinicopathological parameters were analyzed. Survival curves were plotted by using the Kaplan-Meier method， and the survival differences between groups were compared by using the Log-rank test. Considering the significant positive correlation between FOXP3 and LAG-3， a combined immune score （FOXP3 score + LAG-3 score） was constructed. A Cox proportional hazards regression model was used to identify the independent factors that influence long-term prognosis. Results Among the 120 endometrial cancer tissues， the high-expression rates of KIF11， FOXP3， and LAG-3 were 52.50%， 40.83%， and 45.00%， respectively. High KIF11 expression was significantly associated with advanced FIGO stage， deep myometrial invasion， and positive lymphovascular space invasion （all P < 0.05）. High expression of both FOXP3 and LAG-3 was significantly associated with high pathological grade and positive lymph node metastasis （all P < 0.05）， and their expression levels were positively correlated （r = 0.587， P < 0.001）. The areas under the curve （AUCs） of KIF11， FOXP3， and LAG-3 for predicting lymph node metastasis were 0.819， 0.853， and 0.720， respectively. The combined AUC of the three markers was 0.920， which was higher than that of any single indicator （all P < 0.05）. Survival analysis indicated that the 3-year overall survival and disease-free survival rates in the KIF11， FOXP3， and LAG-3 high-expression groups were lower than those in the corresponding low-expression groups （all P < 0.05）. Multivariate Cox regression analysis revealed that high KIF11 expression （HR = 2.18， 95% CI： 1.32 - 3.60）， a higher combined immune score （HR = 1.98， 95% CI： 1.34 - 2.93）， and advanced FIGO stage （HR = 2.54， 95% CI： 1.48 - 4.36） were independent risk factors for overall survival （all P < 0.05）. Conclusion KIF11， FOXP3， and LAG-3 are all abnormally over-expressed in endometrial cancer tissues. These three markers are closely correlated with multiple adverse clinicopathological features and patient prognosis. The combined detection of these three markers demonstrates high discriminatory power for lymph node metastasis. High expression of KIF11 and a higher combined immune score are independent risk factors for long-term prognosis. The positive correlation between FOXP3 and the combined immune score （FOXP3 + LAG-3） implies a potential synergistic effect within the tumor immunosuppressive microenvironment. The combined targeting of KIF11 and immune checkpoint molecules may serve as a novel strategy for the comprehensive treatment of endometrial cancer.

Key words: endometrial cancer, kinesin family member 1, forkhead box protein P3, lymphocyte activation gene-3, prognosis