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

doi:10.3969/j.issn.1006-5725.2026.15.010

Abstract

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

CLC Number:

R737.3

Qiong PENG,Wenyu MU,Shuying CHEN,Tian ZENG. Association of KIF11， FOXP3， and LAG-3 expression with prognosis in endometrial cancer： A retrospective cohort study based on a combined immune score[J]. The Journal of Practical Medicine, 2026, 42(15): 2743-2751.

Figures/Tables 7

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References 26

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临床病理参数	分类	例数	构成比/%
年龄	< 60岁	78	65.00
	≥ 60岁	42	35.00
绝经状态	未绝经	48	40.00
	已绝经	72	60.00
BMI	< 24 kg/m2	55	45.83
	≥ 24k g/m2	65	54.17
FIGO分期	Ⅰ期	58	48.33
	Ⅱ期	32	26.67
	Ⅲ期	22	18.33
	Ⅳ期	8	6.67
病理分级	G1	52	43.33
	G2	42	35.00
	G3	26	21.67
组织学类型	子宫内膜样癌	108	90.00
	非子宫内膜样癌	12	10.00
肌层浸润深度	<1/2	72	60.00
	≥1/2	48	40.00
脉管癌栓	阴性	82	68.33
	阳性	38	31.67
淋巴结转移	阴性	90	75.00
	阳性	30	25.00
腹水细胞学	阴性	104	86.67
	阳性	16	13.33

指标	截断值	敏感度/%	特异度/%	AUC（95% CI）	约登指数	P值
FOXP3	107.96分	86.67	70.00	0.853（0.777 ~ 0.911）	0.5667	< 0.000 1
KIF11	197.99分	63.33	86.67	0.819（0.738 ~ 0.883）	0.5000	< 0.000 1
LAG-3	102.34分	86.67	51.11	0.720（0.631 ~ 0.798）	0.3778	0.000 2
联合诊断	-	76.67	98.89	0.920（0.856 ~ 0.961）	0.7556	< 0.000 1

临床病理参数	例数	KIF11高表达	χ2值	P值	FOXP3高表达	χ2值	P值	LAG-3高表达	χ2值	P值
年龄			0.133	0.716		0.003	0.953		0.001	0.969
< 60岁	78	40（51.28）			32（41.03）			35（44.87）
≥ 60岁	42	23（54.76）			17（40.48）			19（45.24）
绝经状态			0.089	0.765		0.023	0.879		0.022	0.881
未绝经	48	26（54.17）			20（41.67）			22（45.83）
已绝经	72	37（51.39）			29（40.28）			32（44.44）
BMI			0.103	0.748		0.041	0.840		0.008	0.927
< 24 kg/m2	55	28（50.91）			23（41.82）			25（45.45）
≥ 24 kg/m2	65	35（53.85）			26（40.00）			29（44.62）
FIGO分期			12.130	< 0.001		1.391	0.238		2.200	0.138
Ⅰ—Ⅱ期	90	39（43.33）			34（37.78）			37（41.11）
Ⅲ—Ⅳ期	30	24（80.00）			15（50.00）			17（56.67）
病理分级			2.210	0.137		8.281	0.004
G1—G2	94	46（48.94）			32（34.04）			36（38.30）	7.874	0.005
G3	26	17（65.38）			17（65.38）			18（69.23）
组织学类型			1.073	0.300		0.464	0.496		0.958	0.328
内膜样癌	108	55（50.93）			43（39.81）			47（43.52）
非内膜样癌	12	8（66.67）			6（50.00）			7（58.33）
肌层浸润			10.783	0.001		0.828	0.363		0.808	0.369
< 1/2	72	29（40.28）			27（37.50）			30（41.67）
≥ 1/2	48	34（70.83）			22（45.83）			24（50.00）
脉管癌栓			12.648	< 0.001		0.983	0.321		0.562	0.454
阴性	82	34（41.46）			31（37.80）			35（42.68）
阳性	38	29（76.32）			18（47.37）			19（50.00）
淋巴结转移			3.219	0.073		8.382	0.004		7.587	0.006
阴性	90	43（47.78）			30（33.33）			34（37.78）
阳性	30	20（66.67）			19（63.33）			20（66.67）
腹水细胞学			0.870	0.351		0.642	0.423		0.944	0.331
阴性	104	53（50.96）			41（39.42）			45（43.27）
阳性	16	10（62.50）			8（50.00）			9（56.25）

指标	分组	例数	3年OS/%	Log?rank χ2	P值	3年DFS/%	Log?rank χ2	P值
KIF11	高表达	63	68.25	8.64	0.003	60.32	9.87	0.002
	低表达	57	85.96			82.46
FOXP3	高表达	49	67.35	5.23	0.022	59.18	6.18	0.013
	低表达	71	83.10			78.87
LAG-3	高表达	54	64.81	7.45	0.006	57.41	8.92	0.003
	低表达	66	84.85			80.30

变量	单因素分析		多因素分析
变量	HR（95% CI）	P值	HR（95% CI）	P值
年龄（≥ 60岁 vs. < 60岁）	1.28（0.81 ~ 2.02）	0.294	-	-
绝经状态（已绝经 vs. 未绝经）	1.35（0.86 ~ 2.12）	0.196	-	-
BMI（≥ 24 kg/m2 vs. < 24 kg/m2）	1.19（0.76 ~ 1.86）	0.447	-	-
FIGO分期（Ⅲ—Ⅳ期 vs. Ⅰ—Ⅱ期）	3.24（1.98 ~ 5.30）	< 0.001	2.54（1.48 ~ 4.36）	0.001
病理分级（G3 vs. G1—G2）	1.56（0.98 ~ 2.48）	0.062	-	-
组织学类型（非内膜样癌 vs. 内膜样癌）	1.42（0.86 ~ 2.35）	0.173	-	-
肌层浸润深度（≥ 1/2 vs. < 1/2）	2.56（1.58 ~ 4.15）	< 0.001	1.58（0.94 ~ 2.66）	0.085
脉管癌栓（阳性 vs. 阴性）	2.87（1.76 ~ 4.68）	< 0.001	1.62（0.95 ~ 2.76）	0.076
淋巴结转移（阳性 vs. 阴性）	3.12（1.92 ~ 5.07）	< 0.001	1.54（0.89 ~ 2.66）	0.123
腹水细胞学（阳性 vs. 阴性）	1.48（0.92 ~ 2.38）	0.106	-	-
KIF11表达（高表达 vs. 低表达）	2.68（1.64 ~ 4.38）	< 0.001	2.18（1.32 ~ 3.60）	0.002
联合免疫评分（连续，0 ~ 2分）	2.34（1.58 ~ 3.47）	< 0.001	1.98（1.34 ~ 2.93）	0.001
FOXP3表达（高表达 vs. 低表达）	2.13（1.32 ~ 3.44）	0.002	-	-
LAG-3表达（高表达 vs. 低表达）	2.45（1.51 ~ 3.98）	< 0.001	-	-

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

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指标	最小值	最大值	中位数	均数 ± 标准差	高表达例数	高表达率/%
KIF11	45	285	168	169.34 ± 52.18	63	52.50
FOXP3	10	210	95	94.76 ± 41.23	49	40.83
LAG-3	15	230	108	109.22 ± 46.75	54	45.00

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