NLRP1、NLRP3、Caspase-1在子宫内膜异位症中的表达及对预后复发的影响

Expression of NLRP1, NLRP3 and Caspase-1 in endometriosis and their impact on prognosis and recurrence

摘要

目的 探究NLRP1、NLRP3、Caspase-1在不同严重程度子宫内膜异位症(EMS)中的表达及其对预后的影响。方法 选择2017年2月至2020年2月在临沂市人民医院行腹腔镜手术治疗的244例EMS患者为研究组;按临床分期,将患者分为Ⅰ~Ⅱ期162例,Ⅲ~Ⅳ期82例;另选同期因良性卵巢囊肿行腹腔镜手术的77例患者为对照组,对比不同严重程度EMS患者异位内膜组织中NLRP1、NLRP3和Caspase-1的表达情况.将244例EMS患者分为复发组37例与未复发组207例,通过单因素分析,初步筛选EMS患者预后复发的影响因素,且采用多因素Logistic回归分析,进一步筛选独立危险因素.应用Logistic回归模型结合限制性立方样条模型(RCS),分析EMS患者异位内膜组织中NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量与预后复发的剂量-反应关系.依据独立危险因素构建并验证列线图预测模型。结果 EMS患者严重程度分期NLRP1、NLRP3及Caspase-1表达的分布比较,差异均有统计学意义(χ²值分别为9.827、4.916、4.258,P＜0.05);生殖道感染NLRP1、NLRP3及Caspase-1表达的分布比较,差异均有统计学意义(χ²值分别为6.746、13.166、11.643,P＜0.05).研究组不同严重程度异位内膜组织中NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量与对照组比较,差异均有统计学意义(F值分别为18.546、22.582、19.361,P＜0.05).NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量均在研究组Ⅳ期达到最高值,分别为4.30±0.62、5.59±0.77和2.66±0.68.复发组与未复发组的EMS严重程度分期、生殖道感染、术前痛经史的分布比较,差异均有统计学意义(χ²值分别为22.544、18.153、8.882,P＜0.05);复发组与未复发组的C反应蛋白(CRP)、白细胞计数(WBC),以及异位内膜组织中NLRP1 mRNA、NLRP3 mRNA和Caspase-1 mRNA表达量比较,差异均有统计学意义(t值分别为3.727、5.486、13.935、28.167、23.003,P＜0.05).多因素Logistic回归分析显示,EMS严重程度分期(OR＝1.476,95％CI:1.149~1.826)、生殖道感染(OR＝1.256,95％CI:1.028~1.403),以及NLRP1 mRNA(OR＝3.076,95％CI:1.363~4.371)、NLRP3 mRNA(OR＝1.965,95％CI:1.685~2.354)、Caspase-1 mRNA(OR＝2.245,95％CI:1.232~3.152)表达量均是EMS患者预后复发的独立危险因素(P＜0.05).RCS模型分析显示,在NLRP1 mRNA表达量为2.525(OR＝3.076,95％CI:1.363~4.371)、NLRP3 mRNA表达量为3.402(OR＝1.965,95％CI:1.685~2.354)、Caspase-1 mRNA表达量为1.877(OR＝2.245,95％CI:1.232~3.152)处,发生预后复发的风险最大.利用危险因素建立列线图模型,模型具有良好的区分度、准确性。结论 随着NLRP1 mRNA、NLRP3 mRNA及Caspase-1 mRNA表达量的升高,子宫内膜异位症预后复发的危险性随之升高.严重程度分级、生殖道感染,以及NLRP1 mRNA、NLRP3 mRNA、Caspase-1 mRNA表达量均是子宫内膜异位症患者预后复发的独立危险因素.

Abstract

Objective To investigate the expression of NLRP1, NLRP3 and Caspase-1 in endometriosis (EMS) of different severity and their influence on prognosis. Methods A total of 244 patients with endometriosis who underwent laparoscopic surgery in our hospital from January 2017 to January 2020 were selected as the study group, including 162 patients in stage Ⅰ to Ⅱ group, 82 patients in stage Ⅲ to Ⅳ group; the control group consisted of 77 patients with benign ovarian cysts undergoing laparoscopic surgery during the same period. The expressions of NLRP1, NLRP3 and Caspase-1 in three groups were compared. 244 patients with EMS were divided into two groups: recurrence group (n＝37) and non-recurrence group (n＝207). The factors influencing prognosis of EMS patients were preliminarily screened through univariate analysis, and then multivariate Logistic regression analysis was used to further screen independent risk factors. Logistic regression model combined with restricted cubic spline model (RCS) was used to analyze the dose-response relationship between the expressions of NLRP1, NLRP3 and Caspase-1 and prognosis of EMS patients. The nomogram prediction model was constructed and verified according to independent factors. Results There were significant differences in the expression distribution of NLRP1, NLRP3 and Caspase-1 in EMS patients with different severity stages (χ² values were 9.827, 4.916 and 4.258, respectively, P＜0.05). There were significant differences in the distribution of NLRP1, NLRP3 and Caspase-1 expression in EMS patients with and without reproductive tract infection (χ² values were 6.746, 13.166 and 11.643, respectively, P＜0.05). The expressions of NLRP1 mRNA, NLRP3 mRNA and Caspase-1 mRNA in endometrial tissues of different severity of ectopic in the study group were statistically significant compared with those in the control group (F values were 18.546, 22.582 and 19.361, respectively, P＜0.05). The expression levels of NLRP1 mRNA, NLRP3 mRNA, and Caspase-1 mRNA reached their highest values in stage IV of the study group, with values of 4.30±0.62, 5.59±0.77, and 2.66±0.68, respectively. The distribution of EMS severity staging, reproductive tract infection, and preoperative history of dysmenorrhea was significantly different between the recurrence group and the non-recurrence group (χ² values were 22.544, 18.153 and 8.882, respectively, P＜0.05); the levels of CRP, WBC, and the expression of NLRP1 mRNA, NLRP3 mRNA, and Caspase-1 mRNA in ectopic endometrial tissues were significantly different between the recurrence group and the non-recurrence group (t values were 3.727, 5.486, 13.935, 28.167 and 23.003, respectively, P＜0.05). Multivariate logistic regression analysis revealed that EMS severity staging (OR＝1.476, 95％CI: 1.149-1.826), reproductive tract infection (OR＝1.256, 95％CI: 1.028-1.403), and the expression levels of NLRP1 mRNA (OR＝3.076, 95％CI: 1.363-4.371), NLRP3 mRNA (OR＝1.965, 95％CI: 1.685-2.354), and Caspase-1 mRNA (OR＝2.245, 95％CI: 1.232-3.152) were all independent risk factors for recurrence in EMS patients (P＜0.05). RCS model analysis indicated that the highest risk of recurrence occurred at NLRP1 mRNA expression level of 2.525 (OR＝3.076, 95％CI: 1.363-4.371), NLRP3 mRNA expression level of 3.402 (OR＝1.965, 95％CI: 1.685-2.354), and Caspase-1 mRNA expression level of 1.877 (OR＝2.245, 95％CI: 1.232-3.152). The nomogram model was established by using the risk factors. The model has good discrimination and accuracy. Conclusion With the increase of NLRP1 mRNA, NLRP3 mRNA and Caspase-1 mRNA expression levels, the risk of prognosis recurrence of endometriosis increased. The severity grade, reproductive tract infection, NLRP1, NLRP3 and Caspase-1 expression levels are all independent risk factors for the prognosis and recurrence in EMS patients.

关键词

NOD样受体蛋白1 / NOD样受体蛋白3 / 半胱氨酸蛋白酶1 / 子宫内膜异位症 / 预后

Key words

NLRP1 / NLRP3 / Caspase-1 / endometriosis / prognosis

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