宫颈鳞癌组织中miR-448、KDM2B表达水平与术后复发的相关性研究

Correlation between the expression levels of miR-448 and KDM2B in cervical squamous cell carcinoma and postoperative recurrence

目的检测宫颈鳞癌组织中微小RNA-448(miR-448)、赖氨酸特异性脱甲基酶2B(KDM2B)信使核糖核酸(mRNA)和蛋白表达水平与患者术后复发的关系。方法选取2017年8月—2020年3月于榆林市第一医院妇产科行腹腔镜手术及术后病理检查确诊为宫颈鳞癌患者96例为研究对象,根据宫颈鳞癌患者术后18个月内是否复发分为复发组37例和未复发组59例;荧光定量PCR技术检测宫颈鳞癌组织和癌旁正常宫颈组织中miR-448、KDM2B mRNA表达水平,免疫组织化学法检测KDM2B蛋白表达水平;比较2组患者组织中miR-448、KDM2B mRNA和蛋白表达水平;分析宫颈鳞癌组织中miR-448、KDM2B mRNA表达水平的相关性及二者与患者临床病理参数的关系;多因素Logistic回归分析影响宫颈鳞癌患者术后复发的危险因素。结果宫颈鳞癌组织中miR-448表达水平低于正常宫颈组织,KDM2B mRNA表达水平及蛋白阳性表达率高于正常宫颈组织(t/χ^(2)/P=20.487/<0.001、16.292/<0.001、20.023/<0.001);复发组miR-448表达水平低于未复发组,KDM2B mRNA表达水平显著高于未复发组(t/P=7.166/<0.001、5.708/<0.001);肿瘤低中分化、FIGO分期Ⅲ期、有淋巴结转移患者宫颈鳞癌组织中miR-448表达水平明显低于高分化、FIGO分期Ⅰ~Ⅱ期、无淋巴结转移患者(t/P=5.239/<0.001、5.977/<0.001、4.138/<0.001),KDM2B mRNA表达水平明显高于高分化、FIGO分期Ⅰ~Ⅱ期、无淋巴结转移患者(t/P=3.787/<0.001、3.212/0.002、2.255/0.026);宫颈鳞癌组织中miR-448与KDM2B mRNA表达水平呈负相关(r/P=-0.605/<0.001);肿瘤低中分化、FIGO分期Ⅲ期、发生淋巴结转移、miR-448低表达、KDM2B mRNA高表达是影响宫颈鳞癌患者术后发生复发的独立危险因素[OR(95%CI)=2.613(1.377~4.960)、2.537(1.120~5.364)、2.259(1.218~4.188)、3.104(1.471~6.550)、2.948(1.315~6.610)]。结论宫颈鳞癌组织中miR-448表达下调,KDM2B表达上调,二者共同作用参与宫颈鳞癌的发生发展,可能是影响宫颈鳞癌患者术后复发的潜在生物指标。

Objective To detect the relationship between the expression levels of microRNA448(miR-448),lysine-specific demethylase 2B(KDM2B)messenger ribonucleic acid(mRNA)and protein in cervical squamous cell carcinoma and postoperative recurrence of patients.Methods A total of 96 patients with cervical squamous cell carcinoma who underwent laparoscopic surgery and postoperative pathological examination in the Department of Obstetrics and Gynecology of Yulin First Hospital from August 2017 to March 2020 were selected as the research objects.According to whether there was recurrence or not,the patients were divided into a recurrence group of 37 cases and a non-recurrence group of 59 cases.Fluorescence quantitative PCR was used to detect the mRNA expression levels of miR-448 and KDM2B in cervical squamous cell carcinoma tissue and adjacent normal cervical tissue,and immunohistochemistry was used to detect the protein expression level of KDM2B.The mRNA and protein expression levels of miR-448 and KDM2B in the tissues of the two groups were compared.The correlation between the expression levels of miR-448 and KDM2B mRNA in cervical squamous cell carcinoma and their relationship with the clinicopathological parameters of patients were analyzed.Multivariate Logistic regression analysis of risk factors for postoperative recurrence in patients with cervical squamous cell carcinoma.Results The expression level of miR-448 in cervical squamous cell carcinoma tissue was lower than that in normal cervical tissue,and the expression level of KDM2B mRNA and protein were higher than those in normal cervical tissue(t/χ^(2)/P=20.487/<0.001,16.292/<0.001,20.023/<0.001).The expression level of miR-448 in the recurrence group was lower than that in the non-recurrence group,and the expression level of KDM2B mRNA was higher than that in the non-recurrence group(t/P=7.166/<0.001,5.708/<0.001).The expression level of miR-448 in cervical squamous cell carcinoma tissue of patients with low,moderately differentiated tumor,FIGO stage Ⅲ,and lymph node metastasis was significantly lower than that of patients with high differentiation,FIGO stage Ⅰ-Ⅱ,and no lymph node metastasis(t/P=5.239/<0.001,5.977/<0.001,4.138/<0.001),and the KDM2B mRNA expression level was significantly higher than that of well-differentiated patients,FIGO stages Ⅰ-Ⅱ,and no lymph node metastasis(t/P=3.787/<0.001,3.212/0.002,2.255/0.026).The expression levels of miR-448 and KDM2B mRNA in cervical squamous cell carcinoma were negatively correlated(r/P=-0.605/<0.001).Low,moderately differentiated tumor,FIGO stage Ⅲ,lymph node metastasis,low expression of miR-448 and high expression of KDM2B mRNA were independent risk factors for postoperative recurrence in patients with cervical squamous cell carcinoma[OR(95%CI)=2.613(1.377-4.960)],2.537(1.120-5.364),2.259(1.218-4.188),3.104(1.471-6.550),2.948(1.315-6.610)].Conclusion The expression of miR-448 is down-regulated and the expression of KDM2B is up-regulated in cervical squamous cell carcinoma tissue.The two work together are involved in the occurrence and development of cervical squamous cell carcinoma,which may be potential biomarkers for postoperative recurrence of cervical squamous cell carcinoma.