摘要探讨白细胞介素(IL)-1α、IL-1β和IL-1受体拮抗剂(IL-1RN)在宫颈癌组织中的表达及其与宫颈癌临床特征和预后的相关性.方法 于2019年4月28日分别对四个数据库的相关资料进行收集和分析.采用癌症基因组图谱(TCGA)数据库分析宫颈癌组织(292例)IL-1α、IL-1β 和 IL-1RN mRNA 的表达与预后的关系,GEPIA(Gene Expression Profiling Interactive Analysis)数据库(http://gepia.cancer-pku.cn)分析宫颈癌组织(292例)IL-1α、IL-1β和IL-1RN mRNA表达的相关性及与预后的关系,LinkedOmics数据库(http://www.linkedomics.org)分析不同病理类型宫颈癌组织(226例宫颈鳞癌组织和47例宫颈腺癌组织)IL-1α、IL-1β和IL-1RN mRNA的表达情况,STRING数据库(https://string-db.org)分析IL-1α和IL-1β的蛋白互作网络.结果 宫颈癌组织IL-1α、IL-1β和IL-1RN mRNA表达明显高于正常宫颈组织(1.54比0.04、4.82比0.46和73.53比0.67),差异有统计学意义(P＜0.01);Kaplan-Meier生存曲线分析结果显示,IL-1α和IL-1β mRNA高表达提示预后不良(HR=1.7和1.7,P=0.021和0.028),IL-1RN mRNA表达与预后无关(P＞0.05).IL-1α、IL-1β和IL-1RN mRNA的表达两两之间均存在相关性(P＜0.01),以IL-1α和IL-1β的相关性最强(r=0.87,P＜0.01);Kaplan-Meier生存曲线分析结果显示,IL-1α mRNA和IL-1β mRNA联合判定预后的价值最高(HR=2.0).宫颈鳞癌组织IL-1α、IL-1β和IL-1RN mRNA表达明显高于宫颈腺癌组织(6.535比2.936、7.382比5.588和11.170比8.639),差异有统计学意义(P＜0.01).与IL-1α和IL-1β相关的蛋白有白细胞介素1受体1型(IL-1R1)、白细胞介素1受体2型(IL-1R2)、IL-10、IL-4、IL-18、白细胞介素-1受体辅助蛋白(IL1RAP)、肿瘤坏死因子(TNF)、胱天蛋白酶1(CASP1)、IL-8;宫颈癌组织IL1R1 mRNA表达明显低于正常宫颈组织(9.56比40.961), TNF、CASP1、IL1RAP、IL-18和IL-8 mRNA表达明显高于正常宫颈组织(1.51比0.06、33.70比12.61、11.12比3.02、24.59比3.54和20.01比0.48),差异有统计学意义(P＜0.01或＜0.05);其中IL-8 mRNA高表达提示预后不良(HR=2.9,P＜0.01).结论 在宫颈癌发展过程中,IL-1α、IL-1β和IL-1RN的过度表达起着重要作用,IL-1α和IL-1β能够提示宫颈癌的炎性反应和预后,为宫颈癌早期诊断和预后提供理论依据.

abstractsinvestigate the expression of interleukin (IL)-1α, IL-1β and IL-1 receptor antagonist (IL-1RN) in cervical cancer and its correlation with clinical feature and prognosis of cervical cancer. Methods The data of 4 databases were collected and analyzed on April 28, 2019. The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between IL-1α, IL-1β and IL-1RN mRNA expression and prognosis in cervical cancer tissues (292 cases). The GEPIA (Gene Expression Profiling Interactive Analysis) database (http://gepia.cancer-pku.cn) was used to analyze the correlation between IL-1α, IL-1β and IL-1RN mRNA expression and prognosis in cervical cancer tissues (292 cases), the LinkedOmics database (http://www.linkedomics.org) was used to analyze IL-1α, IL-1β and IL-1RN mRNA expression in different pathological types of cervical cancer tissues (226 cervical squamous cell carcinoma tissues and 47 cervical adenocarcinoma tissues), and the STRING database (https://string-db.org) was used to analyze protein interaction networks of IL-1α and IL-1β. Results The expressions of IL-1α, IL-1β and IL-1RN mRNA in cervical cancer tissues were significantly higher than those in normal cervical tissues (1.54 vs. 0.04, 4.82 vs. 0.46 and 73.53 vs. 0.67), and there were statistical differences (P＜0.01); Kaplan-Meier survival curve analysis showed that high expression of IL-1α and IL-1β mRNA suggested poor prognosis (HR=1.7 and 1.7, P=0.021 and 0.028), and IL-1RN mRNA expression was not associated with prognosis (P＞0.05). The expressions of IL-1α, IL-1β and IL-1RN mRNA were correlated between any two indexes (P＜0.01), and the correlation between IL-1α and IL-1β was stronger (r=0.87, P＜0.01); Kaplan-Meier survival curve analysis showed that the assessment prognosis value of IL-1α combined with IL-1β was the highest ( HR=2.0). The expressions of IL-1α, IL-1β and IL-1RN mRNA in cervical squamous cell carcinoma tissues were significantly higher than those in cervical adenocarcinoma tissues (6.535 vs. 2.936, 7.382 vs. 5.588 and 11.170 vs. 8.639), and there were statistical differences (P＜0.01). The associated proteins with IL-1α and IL-1β included IL-1 receptor type 1 (IL-1R1), IL-1 receptor type 2 (IL-1R2), IL-10, IL-4, IL-18, IL-1 receptor accessory protein (IL1RAP), tumor necrosis factor (TNF), caspase 1 (CASP1) and IL-8; IL1R1 mRNA expression in cervical cancer tissues was significantly lower than that in normal cervical tissues (9.56 vs. 40.961), the expressions of TNF, CASP1, IL1RAP, IL-18 and IL-8 mRNA were significantly higher than those in normal cervical tissues (1.51 vs. 0.06, 33.70 vs. 12.61, 11.12 vs. 3.02, 24.59 vs. 3.54 and 20.01 vs. 0.48), and there were statistical differences (P＜0.01 or ＜0.05); high expression of IL-8 mRNA suggested poor prognosis ( HR=2.9, P＜0.01). Conclusions Overexpression of IL-1α, IL-1β and IL-1RN plays an important role in the proliferation of cervical cancer. IL-1α and IL-1β can prompt the inflammatory response and prognosis of cervical cancer, and provide a theoretical basis for the early diagnosis and prognosis of cervical cancer.