宫颈癌术后患者血清IL-1β,MMP-2,25(OH)D表达与下肢深静脉血栓发生的相关性分析

Analysis of correlations of serum IL-1β, MMP-2 and 25(OH)D expressions with lower extremity deep vein thrombosis in patients with cervical cancer after surgery

摘要

目的 探讨宫颈癌(CCA)术后患者血清白细胞介素-1β(IL-1β)、基质金属蛋白酶-2(MMP-2)、25-羟维生素D[25(OH)D]表达与下肢深静脉血栓(DVT)发生的相关性分析。方法 选取2023年6月至2024年6月在秦皇岛市第二医院就诊的104例CCA患者为研究对象,患者均接受腹腔镜手术治疗,根据术后是否发生下肢DVT,将患者分为DVT组43例和非DVT组61例.ELISA法检测血清IL-1β、MMP-2、25(OH)D水平.Pearson法分析CCA术后发生下肢DVT患者血清IL-1β、MMP-2、25(OH)D与DVT指标的相关性;多因素Logistic回归分析CCA患者术后发生下肢DVT的影响因素;受试者工作特征(ROC)曲线分析术后血清IL-1β、MMP-2、25(OH)D水平对CCA患者术后发生下肢DVT的预测价值。结果 与非DVT组相比,DVT组血清IL-1β、MMP-2水平显著较高(t=7.720、8.387,P<0.001),血清25(OH)D水平显著较低(t=7.441,P<0.001);DVT组纤维蛋白原(FIB)和D-二聚体水平显著高于非DVT组(t=7.017、2.502,P<0.05);CCA术后发生下肢DVT患者血清IL-1β、MMP-2与D-二聚体和FIB呈显著正相关(r=0.403、0.328、0.417、0.346,P<0.05),血清25(OH)D与D-二聚体和FIB呈显著负相关(r=-0.451、-0.493,P<0.001);D-二聚体(OR=1.457,95%CI:1.140~1.861)、FIB(OR=1.319,95%CI:1.082~1.608)以及血清IL-1β(OR=2.194,95%CI:1.365~3.526)、MMP-2(OR=2.597,95%CI:1.275~5.290)、25(OH)D(OR=0.762,95%CI:0.619~0.938)是影响CCA患者术后发生下肢DVT的因素(P<0.05);术后血清IL-1β、MMP-2、25(OH)D及三者联合预测CCA患者术后发生下肢DVT的曲线下面积(AUC)分别为0.908、0.846、0.891、0.961,三者联合优于各自单独预测(Z_{三者联合-IL-1β}=2.225、Z_{三者联合-MMP-2}=3.199、Z_{三者联合-25(OH)D}=2.364,P=0.026、0.001、0.018)。结论 CCA术后患者血清IL-1β、MMP-2水平升高,血清25(OH)D水平降低,与下肢DVT发生显著相关,三者联合对CCA患者术后发生下肢DVT有较高的预测价值.

Abstract

Objective To investigate correlations of expressions of interleukin-1β (IL-1β), matrix metalloproteinase-2 (MMP-2) and 25-hydroxyvitamin D [25(OH)D] in serum with occurrence of lower limb deep vein thrombosis (DVT) in patients with cervical cancer (CCA) after surgery. Methods 104 CCA patients who visited to The Second Qinhuangdao Municipal Hospital from June 2023 to June 2024 were selected as research subjects. The patients were treated with laparoscopic surgery. According to whether they developed lower limb DVT after surgery, the patients were assigned into DVT group (n=43) and non-DVT group (n=61). Enzyme-linked immunosorbent assay (ELISA) was applied to detect serum levels of IL-1β, MMP-2 and 25(OH)D. Pearson correlation analysis was used to analyze correlations of serum IL-1β, MMP-2 and 25(OH)D with DVT indexes in patients with lower limb DVT occurred after CCA surgery. Multivariate Logistic regression was applied to analyze influencing factors for lower limb DVT in CCA patients after surgery. Receiver operating characteristic (ROC) curve was applied to analyze predictive values of postoperative serum IL-1β, MMP-2, and 25(OH)D levels for postoperative lower limb DVT in CCA patients. Results Compared with the non-DVT group, the serum IL-1β and MMP-2 levels of the patients in the DVT group were significantly higher (t=7.720 and 8.387 respectively, both P<0.001), while the serum 25(OH)D level was significantly lower (t=7.441, P<0.001). In addition, the levels of fibrinogen (FIB) and D-dimer of the patients in the DVT group were significantly higher than those in the non-DVT group (t=7.017 and 2.502 respectively, both P<0.05). The serum IL-1β and MMP-2 were significantly positively correlated with D-dimer and FIB in the patients with lower extremity DVT after CCA surgery (r=0.403, 0.328, 0.417 and 0.346 respectively, all P<0.05), while serum 25(OH)D was significantly negatively correlated with D-dimer and FIB (r=-0.451 and -0.493 respectively, both P<0.001). D-dimer (OR=1.457, 95%CI: 1.140-1.861), FIB (OR=1.319, 95%CI: 1.082-1.608), serum IL-1β (OR=2.194, 95%CI: 1.365-3.526), MMP-2 (OR=2.597, 95%CI: 1.275-5.290) and 25(OH)D (OR=0.762, 95%CI: 0.619-0.938) were all factors that affected occurrence of lower limb DVT in CCA patients after surgery (all P<0.05). The areas under the curve (AUCs) of postoperative serum IL-1β, MMP-2, 25(OH)D and combination of the three indexes for predicting lower limb DVT in CCA patients were 0.908, 0.846, 0.891 and 0.961 respectively, showing that the predictive value of the combination of the three indexes was better than those of their individual predictions [Z_{combination-IL-1β}=2.225, P=0.026; Z_{combination-MMP-2}=3.199, P=0.001, Z_{combination-25(OH)D}=2.364, P=0.018]. Conclusion After CCA surgery, the serum levels of IL-1β and MMP-2 of the patients increase, while their serum level of 25(OH)D decreases. They are significantly correlated with occurrence of lower limb DVT. The combined detection of the three indexes has high predictive value for occurrence of postoperative lower limb DVT in CCA patients.

关键词

宫颈癌 / 术后 / 下肢深静脉血栓 / 白细胞介素-1β / 基质金属蛋白酶-2 / 25-羟维生素D

Key words

cervical cancer / postoperative period / lower extremity deep vein thrombosis / interleukin-1β / matrix metalloproteinase-2 / 25-hydroxyvitamin D

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基金资助

河北省2023年度医学科学研究项目(20231894)