宫颈癌病人血清微小RNA-145表达及与人乳头瘤病毒16型感染的关系

Expression of miR-145 in serum of patients with cervical cancer and its relationship with HPV16 infection

目的探究宫颈癌病人血清微小RNA-145(miR-145)与人乳头瘤病毒16型(HPV16)感染相关性。方法选取2015年5月至2019年5月三亚市中医院收治的宫颈癌病人83例,另选取同期在该院体检显示健康者83例为对照组。采用实时荧光定量PCR(qRT-PCR)检测所有入组者血清miR-145表达水平,采用多重PCR技术检测宫颈脱落细胞人乳头瘤病毒16型E6蛋白(HPV16 E6)DNA表达水平,采用logistic回归模型进行危险因素分析,采用Pearson法进行相关性分析,采用受试者工作特征曲线(ROC曲线)进行miR-145诊断价值分析。结果宫颈癌组病人流产次数>1比例、宫颈脱落细胞HPV16阳性率及HPV16 E6 mRNA表达水平显著高于对照组(P<0.05)。宫颈癌组血清miR-145水平(0.37±0.11)显著低于对照组(1.02±0.31)(P<0.05)。宫颈癌高、中、低分化病人血清miR-145水平分别为(0.42±0.16)、(0.35±0.12)、(0.33±0.08),不同分化程度病人血清miR-145水平比较,差异有统计学意义(P<0.05)。FIGO分期Ⅰ-Ⅱ期、Ⅲ/Ⅵ期病人血清miR-145水平分别为(0.45±0.14)及(0.29±0.07),有淋巴结转移及无淋巴结转移病人血清miR-145水平分别为(0.47±0.18)及(0.31±0.08),HPV16阴性及阳性病人血清miR-145水平分别为(0.44±0.15)及(0.32±0.09),FIGO分期Ⅲ/Ⅵ期、有淋巴结转移、HPV16阳性病人血清miR-145水平明显低于FIGO分期Ⅰ/Ⅱ期、无淋巴结转移、HPV16阴性病人(P<0.05)。宫颈癌病人血清miR-145与宫颈脱落细胞中HPV16 E6 mRNA表达水平呈负相关(r=−0.372,P<0.05)。流产次数>1、HPV16阳性、miR-145低表达是影响宫颈癌发生独立危险因素(P<0.05)。结论宫颈癌病人血清miR-145水平降低,宫颈脱落细胞HPV16阳性及HPV16 E6 mRNA表达水平升高;miR-145通过与HPV16相互作用,影响宫颈癌发生发展。

Objective To investigate the correlation between microRNA-145(miR-145)and human papillomavirus(HPV)infection in patients with cervical cancer.Methods From May 2015 to May 2019,83 patients with cervical cancer admitted to Sanya Hospital of Traditional Chinese Medicine were selected as the research objects,in addition,the healthy persons who were examined in the hospi⁃tal in the same period were selected as the control group.The expression of miR-145 in serum was detected by quantitative real-time polymerase chain reaction(qRT-PCR),and the expression of HPV16 E6 DNA in cervical exfoliated cells was detected by multiplex polymerase chain reaction(Multiplex PCR).Logistic regression model was used to analyze the risk factors.Pearson method was used to analyze the correlation,and ROC curve was used to analyze the diagnostic value of miR-145.Results The percentage of patients with abortion times>1,the positive rate of HPV16 and the expression level of HPV16 E6 mRNA in cervical exfoliated cells in cervical can⁃cer group were significantly higher than those in the control group(P<0.05).The level of serum miR-145 in cervical cancer group(0.37±0.11)was significantly lower than that in control group(1.02±0.31),and the difference was statistically significant(P<0.05).The levels of serum miR-145 in patients with high,medium and low differentiation of cervical cancer were(0.42±0.16),(0.35±0.12)and(0.33±0.08)respectively,and the differences were statistically significant(P<0.05).The serum levels of miR-145 were(0.45±0.14)and(0.29±0.07)in FIGO stage I-II and III/VI patients,respectively.The serum levels of miR-145 in patients with lymph node metasta⁃sis and without lymph node metastasis were(0.47±0.18)and(0.31±0.08)respectively.The serum levels of miR-145 in HPV16 negative and positive patients were(0.44±0.15)and(0.32±0.09),respectively.The levels of miR-145 in patients with FIGO stageⅢ-Ⅵ,lymph node metastasis and HPV16 positive were significantly lower than those in patients with FIGO stageⅠ-Ⅱ,no lymph node metastasis and HPV16 negative(P<0.05).The expression of serum miR-145 was negatively correlated with HPV16 E6 mRNA in cervical exfoli⁃ated cells(r=−0.372,P<0.05).Abortion frequency>1,positive HPV16 and miR-145 low expression were independent risk factors for cervical cancer(P<0.05).Conclusion The level of miR-145 in patients with cervical cancer is lower,the positive of HPV16 and the expression level of HPV16 E6 mRNA in cervical exfoliated cells are higher,and miR-145 affects the development of cervical can⁃cer through interaction with HPV16.