MicroRNA-129-5p、SOX4在宫颈癌组织中的表达及其与患者临床病理特征、预后的关系

Expression of microRNA-129-5p and SOX4 in cervical cancer tissues and their relationship with clinicopathological characteristics and prognosis of patients

摘要:

目的 探讨宫颈癌组织中microRNA-129-5p（miR-129-5p）、性别决定区Y框蛋白4（SOX4）表达与临床病理特征及预后的关系。方法 选取2017年6月—2019年8月湖北民族大学附属民大医院101例宫颈癌患者的宫颈癌组织、癌旁组织标本及其临床资料，根据患者生存情况将其分为生存组79例和死亡组22例。采用免疫组织化学法检测SOX4蛋白阳性表达，采用实时荧光定量聚合酶链反应（qRT-PCR）检测miR-129-5p mRNA相对表达量。绘制Kaplan-Meier曲线分析miR-129-5p、SOX4表达与宫颈癌患者3年生存率的关系；采用多因素Cox回归分析宫颈癌患者预后的影响因素。结果 宫颈癌组织miR-129-5p mRNA相对表达量低于癌旁组织（P <0.05），SOX4蛋白阳性表达率高于癌旁组织（P <0.05）。FIGO分期Ⅱ期、低分化、有淋巴结转移的宫颈癌患者组织中miR-129-5p高表达、SOX4蛋白阳性表达率高于FIGO分期Ⅰ期、中/高分化、无淋巴结转移患者（P <0.05）。miR-129-5p低表达患者3年生存率低于miR-129-5p高表达患者（P <0.05）；SOX4蛋白阳性表达患者3年生存率低于SOX4蛋白阴性表达患者（P <0.05）。死亡组FIGO分期Ⅱ期患者比例高于生存组（P <0.05）。SOX4蛋白阳性表达［H^R=2.793（95%CI：1.495，5.219）］是宫颈癌患者3年内死亡的危险因素，miR-129-5p高表达［H^R=0.809（95%CI：0.700，0.935）］是宫颈癌患者3年内死亡的保护因素（P <0.05）。结论 宫颈癌组织中miR-129-5p表达降低、SOX4表达升高，两者表达与FIGO分期、分化程度、淋巴结转移及3年预后有关，有可作为预后评估的生物标志物。

Abstract:

Objective To investigate the relationship between the expression levels of microRNA-129-5p (miR-129-5p) and sex-determining region Y-box protein 4 (SOX4) in cervical cancer tissue with clinicopathological features and prognosis.Methods From June 2017 to August 2019, 101 cervical cancer tissue, paracancerous tissue specimens, and clinical data of cervical cancer patients in Affiliated Minzu University Hospital of Hubei Minzu University were collected. According to the survival of the patients, they were grouped into a survival group of 79 cases and a death group of 22 cases. Immunohistochemistry was used to measure the SOX4 level, and quantitative real-time PCR (qRT-PCR) was used to measure miR-129-5p level. Kaplan-Meier curve was drawn to analyze the relationship of the expression levels of miR-129-5p and SOX4 with the 3-year survival rate of cervical cancer patients. Multivariate Cox regression was used to analyze prognostic factors in cervical cancer patients.Results The level of miR-129-5p in cervical cancer tissue was lower than that in adjacent tissue (P < 0.05), and the positive rate of SOX4 was higher than that in adjacent tissue (P < 0.05). The high expression of miR-129-5p and the positive proportion of SOX4 in the tissues of cervical cancer patients with FIGO stage Ⅱ, low differentiation, and lymph node metastasis were significantly higher than those of patients with FIGO stage Ⅰ, medium/high differentiation, and no lymph node metastasis（P < 0.05). The 3-year survival rate of patients with low miR-129-5p expression was lower than that of patients with high miR-129-5p expression (P < 0.05), and the 3-year survival rate of SOX4-positive patients was lower than that of SOX4-negative patients (P < 0.05). The proportions of patients with FIGO stage Ⅱ in the death group were higher than those in the survival group (P < 0.05). SOX4 positive expression [H^R = 2.793 (95% CI: 1.495, 5.219) ] is a risk factor for death of cervical cancer patients within 3 years, and miR-129-5p high expression [H^R = 0.809 (95% CI: 0.700, 0.935) ] is a protective factor for death of cervical cancer patients within 3 years (P < 0.05).Conclusion The expression of miR-129-5p is down-regulated and the expression of SOX4 is up-regulated in cervical cancer tissue. The expression levels of the two are related to the depth of myometrial invasion, FIGO stage, lymph node metastasis, and 3-year prognosis, which can be used as biomarkers for prognosis evaluation.