肿瘤诊治与预后专栏

子宫内膜癌组织KIF11、FOXP3、LAG-3表达与预后的关系:基于联合免疫评分的回顾性队列研究

  • 彭琼 ,
  • 穆文玉 ,
  • 陈书英 ,
  • 曾田
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  • 徐州医科大学附属医院妇产科 (江苏 徐州 221000 )

收稿日期: 2026-04-08

  修回日期: 2026-06-12

  录用日期: 2026-06-16

  网络出版日期: 2026-08-13

基金资助

江苏省妇幼健康科研项目(F202002)

Association of KIF11, FOXP3, and LAG-3 expression with prognosis in endometrial cancer: A retrospective cohort study based on a combined immune score

  • Qiong PENG ,
  • Wenyu MU ,
  • Shuying CHEN ,
  • Tian ZENG
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  • Department of Obstetrics and Gynecology,Xuzhou Medical University Affiliated Hospital,Xuzhou 221000,Jiangsu,China

Received date: 2026-04-08

  Revised date: 2026-06-12

  Accepted date: 2026-06-16

  Online published: 2026-08-13

摘要

目的 探讨子宫内膜癌组织中驱动蛋白家族成员11(KIF11)、叉头框蛋白P3(FOXP3)及淋巴细胞活化基因-3(LAG-3)的表达水平与患者临床病理特征及远期预后的相关性。 方法 回顾性收集2019年1月至2022年12月期间收治的120例子宫内膜癌患者的临床病理资料及石蜡包埋组织标本。采用免疫组化法检测癌组织中KIF11、FOXP3及LAG-3表达,并进行H-score评分。以淋巴结转移状态为状态变量绘制受试者工作特征(ROC)曲线,分析各指标区分淋巴结转移的诊断效能,并根据约登指数确定最佳截断值,将患者分为高、低表达组。分析三者表达与临床病理参数的关系;采用Kaplan?Meier法绘制生存曲线,Log?rank检验比较组间生存差异;鉴于FOXP3与LAG-3呈正相关,构建联合免疫评分(FOXP3赋分 + LAG-3赋分),采用Cox比例风险回归模型筛选影响患者远期预后的独立危险因素。 结果 120例子宫内膜癌组织中,KIF11、FOXP3、LAG-3高表达率分别为52.50%、40.83%与45.00%。KIF11高表达与FIGO分期晚、深肌层浸润及脉管癌栓阳性有相关性(P < 0.05);FOXP3与LAG-3高表达均与病理分级高及淋巴结转移阳性有相关性(P < 0.05),且二者表达呈正相关(r = 0.587,P < 0.001)。KIF11、FOXP3、LAG-3预测淋巴结转移AUC分别为0.819、0.853与0.720,三者联合预测AUC为0.920,高于任一单项指标(P < 0.05)。生存分析显示,KIF11、FOXP3、LAG-3高表达组3年总生存率与无病生存率均低于低表达组(P < 0.05)。多因素Cox回归分析显示,KIF11高表达(HR = 2.18,95% CI:1.32 ~ 3.60)、联合免疫评分越高(HR = 1.98,95% CI:1.34 ~ 2.93)及FIGO分期晚(HR = 2.54,95% CI:1.48 ~ 4.36)是影响患者总生存的独立危险因素(P < 0.05)。 结论 KIF11、FOXP3及LAG-3在子宫内膜癌组织中均存在异常高表达,三者与多项不良临床病理特征及患者预后密切相关。三者联合检测对淋巴结转移具有较高的鉴别能力,KIF11高表达及较高的联合免疫评分(FOXP3与LAG-3联合)是影响患者远期预后的独立危险因素。FOXP3与LAG-3的表达正相关性提示肿瘤免疫抑制微环境可能存在协同作用。

本文引用格式

彭琼 , 穆文玉 , 陈书英 , 曾田 . 子宫内膜癌组织KIF11、FOXP3、LAG-3表达与预后的关系:基于联合免疫评分的回顾性队列研究[J]. 实用医学杂志, 2026 , 42(15) : 2743 -2751 . DOI: 10.3969/j.issn.1006-5725.2026.15.010

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.

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