早期宫颈癌患者血清HMGB1、TLR4和RAGE4水平对肿瘤恶性生物学行为的指向性研究

Directional study of serum HMGB1,TLR4 and RAGE4 levels on malignant biological behavior of early-stage cervical cancer

目的分析早期宫颈癌血清HMGB1、TLR4和RAGE4水平对肿瘤恶性生物学行为的指向性评估价值。方法选取2016年3至2019年6月确诊的早期宫颈癌患者139例,对患者进行病理诊断并分期,取患者研究期1周内晨起空腹静肘脉血,以酶联免疫吸附的方式检测患者血清肿瘤局部免疫状态炎性因子(HMGB1、TLR4和RAGE4)和肿瘤恶性生物学行为调控因子(Caspase-3、bcl-2、MMP-1)水平。评估血清HMGB1、TLR4和RAGE4水平对早期宫颈癌分期的预评估效能。进一步分析HMGB1、TLR4和RAGE4与Caspase-3、bcl-2、MMP-1指标间的量化相关性。结果分期组间各因子水平比较结果显示,Ⅰa期与Ⅰb期、Ⅰa期与Ⅱa期患者血清肿瘤局部免疫状态炎性因子(HMGB1、TLR4和RAGE4)和肿瘤恶性生物学行为调控因子(Caspase-3、bcl-2、MMP-1)水平差异均有统计学意义(P<0.05);ROC曲线分析结果提示,HMGB1对早期宫颈癌Ⅰa期与Ⅰb期具有较高的预测鉴别诊断价值,曲线下面积为0.939,诊断临界值为0.83 ng/mL(灵敏度为97.62%,特异度为86.60%)。血清肿瘤局部免疫状态炎性因子与肿瘤恶性生物学行为调控因子水平相关分析结果显示,各因子水平均呈现高度正相关,相关系数0.715~0.854。结论早期宫颈癌患者血清局部免疫状态炎性反应因子对肿瘤恶性生物学行为具有一定的定性与定量指向性预测诊断价值,与恶性生物学行为相关因子水平高度相关。

Objective To analyze the directional evaluation values of serum high-mobility group box 1(HMGB1),Toll like receptor-4(TLR4)and RAGE4 levels on malignant biological behavioRof early-stage cervical cancer.Methods A total of 139 patients diagnosed with early-stage cervical cancer from March 2016 to June 2019 were selected.They were assessed for pathological diagnosis and tumoRstaging.Fasting elbow vein blood was taken in the morning within one week of the study period,and serum levels of local immune status inflammatory factors in the tumoR(HMGB1,TLR4 and RAGE4)and regulatory factors for malignant behaviors(Caspase-3,bcl-2,matrix metalloproteinase-1[MMP-1])were detected by enzyme-linked immunosorbent assay(ELISA).The predictive efficacy of serum HMGB1,TLR4 and RAGE4 levels for tumoRstaging of early-stage cervical cancer was analyzed.The quantitative correlations of HMGB1,TLR4 and RAGE4 with Caspase-3,Bcl-2 and MMP-1 were further analyzed.Results There were significant differences in the serum levels of local immune status inflammatory factors in the tumoR(HMGB1,TLR4 and RAGE4)and regulatory factors for malignant behaviors(Caspase-3,bcl-2,MMP-1)between cervical cancer patients with stageⅠa versusⅠb,and those with stageⅠa versusⅡa(P<0.05).The receiveRoperating characteristic(ROC)curve analysis showed that HMGB1 had a high value in predicting and differentiating early-stage cervical cancer with stageⅠa andⅠb.The area undeRthe curve(AUC)of HMGB1 in predicting stageⅠa andⅠb cervical cancer was 0.939,with the optimal cut-off value,sensitivity and specificity of 0.83ng/mL,97.62%and 86.60%,respectively.Correlation analysis showed that local immune status inflammatory factors were highly positively correlated with regulatory factors for malignant behaviors,with the correlation coefficient ranging from 0.715 to 0.854.Conclusion Serum local inflammatory factors in patients with early cervical cancer have certain qualitative and quantitative directional predictive diagnostic values for malignant behaviors.They are highly correlated with the levels of factors related to malignant behaviors.