血清NLRP3炎症小体水平与HPV感染及宫颈癌临床病理特征的相关性分析

Correlation analysis of serum NLRP3 inflammasome level with HPV infection and clinicopathologicalfeatures of cervical cancer

目的:分析血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体及其下游炎症因子白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)水平与人乳头瘤病毒(HPV)感染及宫颈癌临床病理特征的相关性。方法:选取2019年1月至2022年6月广西壮族自治区民族医院收治的180例宫颈癌患者为研究对象(宫颈癌组),另取同期在本院体检中心行体格检查的180例女性健康志愿者作为对照组。采用酶联免疫吸附试验(ELISA)法检测血清NLRP3、IL-18、IL-1β水平。应用基因扩增技术和导流杂交检测宫颈HPV-DNA分型,受试者工作特征(ROC)曲线评估NLRP3、IL-18、IL-1β及联合检测对宫颈癌的诊断价值,Spearman秩相关分析方法分析NLRP3与IL-18、IL-1β、HPV感染及临床病理特征之间的关系。结果:宫颈癌组NLRP3、IL-1β水平明显高于对照组(P<0.05),但两组IL-18水平差异无统计学意义(P>0.05)。NLRP3、IL-18、IL-1β单独诊断宫颈癌的ROC曲线下面积(AUC)分别为0.67、0.57、0.62,均低于3个指标联合检测的AUC(0.78)。宫颈癌组NLRP3水平与IL-18、IL-1β水平均呈正相关关系(r=0.867,r=0.831,均P<0.001)。宫颈癌组HPV感染者NLRP3、IL-18、IL-1β水平高于无HPV感染者(P<0.05)。宫颈癌组临床分期和分化程度越高,血清NLRP3、IL-18、IL-1β水平越高(均P<0.05)。结论:血清NLRP3炎症小体、IL-18和IL-1β水平可能与HPV感染及宫颈癌的发生、发展密切相关,这一结论可能为宫颈癌分子靶向治疗提供新的思路。

Objective:To analyze the correlation between serum of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome and its downstream inflammatory factors interleukin-18(IL-18)and interleukin-1β(IL-1β)levels with human papillomavirus(HPV)infection and clinicopathological features of cervical cancer.Methods:A total of 180 patients with cervical cancer admitted to the Minzu Hospital of Guangxi Zhuang Autonomous Region from January 2019 to June 2022 were selected as the study subjects(cervical cancer group),and 180 healthy female volunteers who underwent physical examination in the physical examination cen-ter in the hospital during the same period were selected as the control group.Serum levels of NLRP3,IL-18 and IL-1βwere detected by enzyme-linked immunosorbent assay(ELISA).Cervical HPV-DNA typing was detected by gene amplification and flow-through hybridization.The receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic value of NLRP3,IL-18 as well as IL-1βand their combined detection in cervi-cal cancer.The relationship between NLRP3 and IL-18,IL-1β,HPV infection and clinicopathological features was analyzed by Spearman rank correlation.Results:The levels of NLRP3 and IL-1βin the cervical cancer group were significantly higher than those in the control group(P<0.05),while there was no significant differ-ence in IL-18 level between the two groups(P>0.05).The area under ROC curve(AUC)of NLRP3,IL-18 and IL-1βalone in the diagnosis of cervical cancer were 0.67,0.57 and 0.62,respectively,all of which were lower than the AUC for the combined detection of the three indicators(0.78).The level of NLRP3 was positively correlated with the levels of IL-18 and IL-1β(r=0.867,r=0.831,both P<0.001).The levels of NLRP3,IL-18 and IL-1βin HPV-infected patients were higher than those in non-HPV-infected patients(P<0.05).The higher the clinical stage and differentiation degree of cervical cancer group,the higher the levels of serum NLRP3,IL-18 and IL-1β(all P<0.05).Conclusion:Serum NLRP3 inflammasome,IL-18 and IL-1βlevels may be closely related to HPV infection and the occurrence and development of cervical cancer.This conclusion may provide a new idea for molecular targeted therapy of cervical cancer.