网膜素-1、分泌型磷蛋白1、错配修复系统蛋白表达状态与子宫内膜癌患者临床病理特征及预后的关系

doi:10.3969/j.issn.1006-5725.2025.16.012

摘要/Abstract

摘要：

目的通过免疫组化检测探讨网膜素-1（omentin-1）、分泌型磷蛋白1（SPP1）、错配修复系统（MMR）蛋白表达状态对子宫内膜癌（EC）临床病理特征的影响及预后变化。方法选取我院2019年12月至2021年12月收治的EC患者159例作为观察组，选取同时期因子宫良性疾病切除子宫的患者的正常内膜组织152例作为对照组。比较观察组、对照组以及不同临床病理特征、预后EC患者子宫内膜组织omentin-1、SPP1、MMR蛋白表达情况，通过Spearman相关分析法分析各指标在EC组织中表达的相关性，通过多因素logistic回归分析EC预后的影响因素，绘制Kaplan-Meier生存曲线分析组织指标与EC预后的关系。结果观察组子宫内膜组织SPP1阳性、MMR缺失率高于对照组（P < 0.05），子宫内膜组织omentin-1阳性率低于对照组（P < 0.05）。肌层浸润≥ 1/2的EC患者omentin-1阴性比例低于Omentin-1阳性（P < 0.05）；分化程度为低分化的EC患者SPP1阳性、MMR缺失占比更高（P < 0.05）。通过Spearman相关分析法结果显示，omentin-1蛋白阳性与MMR蛋白缺失、SPP1蛋白阳性表达呈负相关（P < 0.05），MMR蛋白缺失与SPP1蛋白阳性表达呈正相关（P < 0.05）。预后不良组子宫内膜组织SPP1阳性、MMR缺失率更高，子宫内膜组织omentin-1阳性率更低（P < 0.05）。多因素logistic分析结果显示，omentin-1阴性、SPP1阳性、MMR缺失为EC患者预后不良的危险因素（P < 0.05）。根据随访资料绘制Kaplan-Meier生存曲线，由生存曲线可知omentin-1蛋白阴性、SPP1蛋白阳性、MMR蛋白缺失患者预后较差，差异有统计学意义（P < 0.05）。结论随着EC发生及临床病理特征进展，免疫组化检测omentin-1、SPP1、MMR蛋白表达存在异常，omentin-1蛋白阴性、SPP1蛋白阳性、MMR蛋白缺失与EC预后不良有关且为其独立危险因素。

关键词: 子宫内膜癌, 免疫组化, 网膜素-1, 分泌型磷蛋白1, 错配修复系统, 临床病理特征, 预后

Abstract:

Objective To investigate the impact of immunohistochemical detection of omentin-1 （omentin-1）， secreted phosphoprotein 1 （SPP1）， and mismatch repair （MMR） protein expression status on the clinicopathological characteristics and prognosis of endometrial cancer （EC）， in order to provide references for disease assessment， prognosis evaluation， and the development of molecular targeted therapies. Methods A total of 159 patients diagnosed with EC who were admitted to our hospital between December 2019 and December 2021 were enrolled as the study group. Additionally， 152 samples of normal endometrial tissue were collected from patients undergoing hysterectomy due to benign uterine diseases and served as the control group. The expression levels of omentin-1， SPP1， and MMR proteins in endometrial tissues were compared among the study group， the control group， and EC patients with different clinicopathological characteristics and prognostic outcomes. Spearman correlation analysis was performed to evaluate the correlations among these biomarkers in EC tissues. The influencing factors of EC prognosis were analyzed through multivariate logistic regression. Kaplan-Meier survival curves were constructed to assess the association between the expression of these proteins and patient prognosis. Results The positive expression rate of SPP1 and the MMR deletion rate in endometrial tissues of the study group were significantly higher than those in the control group （P < 0.05）， while the positive expression rate of omentin-1 in endometrial tissues was significantly lower than that in the control group （P < 0.05）. In patients with EC exhibiting myometrial invasion ≥1/2， the proportion of omentin-1 negativity was lower compared to omentin-1 positivity （P < 0.05）. Among EC patients with poorly differentiated tumors， the rates of SPP1 positivity and MMR deficiency were significantly increased （P < 0.05）. Spearman correlation analysis revealed that omentin-1 expression was negatively correlated with both MMR protein deletion and SPP1 overexpression （P < 0.05）， whereas MMR deficiency was positively correlated with SPP1 overexpression （P < 0.05）. In the poor prognosis group， the positive expression rate of SPP1 and the deletion rate of MMR were elevated， while omentin-1 expression was reduced in endometrial tissues （P < 0.05）. The results of multivariate logistic analysis showed that omentin-1 negative， SPP1 positive， and MMR deletion were risk factors for the prognosis of EC patients （P<0.05）. Kaplan-Meier survival curves were constructed based on follow-up data （Figures 1–3）， indicating that patients with omentin-1 negativity， SPP1 positivity， and MMR deficiency had significantly worse prognoses （P< 0.05）. Conclusions With the development and progression of the clinicopathological features of EC， abnormalities were observed in the immunohistochemical expression of omentin-1， SPP1， and MMR proteins. Specifically， omentin-1 negativity， SPP1 positivity， and MMR protein deletion were associated with a poorer prognosis in EC patients.

Key words: endometrial cancer, immunohistochemistry, omentin-1, secreted phosphoprotein 1, mismatch repair, clinicopathological features, prognosis

中图分类号:

R737.33

徐西凤,王侠,吴健亮,程金龙. 网膜素-1、分泌型磷蛋白1、错配修复系统蛋白表达状态与子宫内膜癌患者临床病理特征及预后的关系[J]. 实用医学杂志, 2025, 41(16): 2521-2527.

Xifeng XU,Xia WANG,Jianliang WU,Jinlong. CHENG. Effect of immunohistochemical detection of omentin-1， SPP1 and MMR protein expression status on clinicopathological features and prognosis analysis of endometrial cancer[J]. The Journal of Practical Medicine, 2025, 41(16): 2521-2527.

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指标	观察组(n = 152)	对照组(n = 152)	χ² 值	P值
omentin-1阳性	48(31.58)	103(67.76)	39.804	< 0.001
SPP1阳性	107(70.39)	53(34.87)	38.475	< 0.001
MMR缺失	58(38.16)	7(4.61)	50.898	< 0.001

组别	例数	omentin-1		χ² 值	P值	SPP1		χ² 值	P值	MMR		χ² 值	P值
组别	例数	阳性 (n = 48)	阴性 (n = 104)	χ² 值	P值	阳性 (n = 107)	阴性 (n = 45)	χ² 值	P值	缺失 (n = 58)	完整 (n = 94)	χ² 值	P值
FIGO分期				0.780	0.377			0.935	0.333			0.543	0.461
Ⅰ/Ⅱ期	110	37(77.08)	73(70.19)			75(70.09)	35(77.78)			40(68.97)	70(74.47)
Ⅲ/Ⅳ期	42	11(22.92)	31(29.81)			32(29.91)	10(22.22)			18(31.03)	24(25.53)
分化程度				0.031	0.860			15.952	< 0.001			16.304	< 0.001
中高分化	103	33(68.75)	70(67.31)			62(57.94)	41(91.11)			28(48.28)	75(79.79)
低分化	49	15(31.25)	34(32.69)			45(42.06)	4(8.89)			30(51.72)	19(20.21)
淋巴结转移				0.417	0.518			0.155	0.694			0.424	0.515
无	122	40(83.33)	82(78.85)			85(79.44)	37(82.22)			45(77.59)	77(81.91)
有	30	8(16.67)	22(21.15)			22(20.56)	8(17.78)			13(22.41)	17(18.09)
肌层浸润				28.453	< 0.001			0.912	0.340			0.243	0.622
< 1/2	72	38(79.17)	34(32.69)			48(44.86)	24(53.33)			26(44.83)	46(48.94)
≥ 1/2	80	10(20.83)	70(67.31)			59(55.14)	21(46.67)			32(55.17)	48(51.06)

指标	omentin-1蛋白阳性		SPP1蛋白阳性
指标	r值	P值	r值	P值
MMR蛋白缺失	-0.687	0.011	0.876	< 0.001
omentin-1蛋白阳性	-	-	-0.760	< 0.001

变量	β	SE	Wald χ²	P值	OR	95%CI
omentin-1阴性	0.591	0.268	4.863	0.027	1.806	1.068 ~ 3.053
SPP1阳性	0.673	0.298	5.100	0.024	1.960	1.093 ~ 3.515
MMR缺失	0.742	0.281	6.973	0.008	2.100	1.211 ~ 3.643