高危型HPV阳性宫颈癌患者miRNA-34a-5p的表达及临床意义

Expression and clinical significance of miRNA-34a-5p in patients with high-risk HPV-positive cervical cancer

目的探讨高危型人乳头状瘤病毒(high risk-human papilloma virus,HR-HPV)阳性宫颈癌患者组织及血清中微小RNA(microRNA,miRNA)-34a-5p的表达及其对宫颈癌的诊断价值。方法将100例HR-HPV阳性宫颈癌患者(宫颈癌组)、70例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)患者(CIN组)、70例HR-HPV阳性子宫良性病变或者HPV单纯阳性的健康体检者(对照组)作为研究对象。采集上述研究对象的血清标本及70例行手术治疗的宫颈癌组患者癌组织及癌旁组织。使用实时荧光定量PCR技术测定组织及血清中miRNA-34a-5p水平,并分析miRNA-34a-5p与宫颈癌临床、病理指标的关联及血清miRNA-34a-5p对宫颈癌的诊断价值。结果①对照组血清中miRNA-34a-5p的相对表达量高于CIN组和宫颈癌组:(0.933±0.097)vs.(0.554±0.099)vs.(0.369±0.099),差异有统计学意义(F=741.401,P=0.000);宫颈癌组患者术前血清中miRNA-34a-5p相对表达量低于术后1周,差异有统计学意义(t=8.305,P=0.000)。有无淋巴结转移和有无远处转移的宫颈癌患者血清中miRNA-34a-5p相对表达量的差异有统计学意义(P均<0.05)。②宫颈癌组患者癌旁组织中miRNA-34a-5p的相对表达量高于癌组织,差异具有统计学意义(t=40.313,P=0.000)。③宫颈癌组患者癌组织中的miRNA-34a-5p表达水平与血清中的表达水平呈正相关(r=0.908,P=0.000)。④以0.508为miRNA-34a-5p相对表达量的最佳临界值诊断宫颈癌,其灵敏度为83.6%,特异度为79.4%,AUC为0.860,95%置信区间为0.803~0.917。结论HR-HPV阳性宫颈癌患者癌组织和血清中miRNA-34a-5p表达下调,对宫颈癌诊断及预后监测具有一定的参考价值。

Objective To investigate the expression of microRNA(miRNA)-34a-5p in tissues and serum of patients with high-risk human papilloma virus(HR-HPV)-positive cervical cancer,and explore the diagnostic value of miRNA-34a-5p for cervical cancer.Methods One hundred patients with HR-HPV-positive cervical cancer(cervical cancer group),70 patients with cervical intraepithelial neoplasia(CIN)(CIN group)and 70 healthy examinees(control group)with HR-HPV positive uterine benign lesions or HPV simple positive were taken as the research objects.Serum specimens of the above research subjects and the cancer tissues and adjacent tissues of 70 patients with cervical cancer undergoing surgical treatment were collected.Real-time fluorescence quantitative PCR was used to determine miRNA-34a-5p levels in tissue and serum,and to analyze the correlation of clinical and pathological indicators of cervical cancer with miRNA-34a-5p and the diagnostic value of serum miRNA-34a-5p for cervical cancer.Results The relative expression of miRNA-34a-5p in the serum of the control group was higher than that of the CIN group and the cervical cancer group:(0.933±0.097)vs.(0.554±0.099)vs.(0.369±0.099),the difference was statistically significant(F=741.401,P=0.000).The relative expression of serum miRNA-34a-5p in patients with cervical cancer before operation was lower than that after operation,and the difference was statistically significant(t=8.305,P=0.000).There were significant differences in serum miRNA-34a-5p relative expression of cervical cancer patients with or without lymph node metastasis and with and without distant metastasis(all P<0.05);②The relative expression of miRNA-34a-5p in adjacent tissues in cervical cancer group was higher than that in cancer tissues,and the difference was statistically significant(t=40.313,P=0.000);③The expression level of miRNA-34a-5p in cancer tissues and serum of cervical cancer patients was positively correlated(r=0.908,P=0.000);④The optimal cutoff value of the relative expression level of miRNA-34a-5p was 0.508 for the diagnosis of cervical cancer.The sensitivity was 83.6%,the specificity was 79.4%,the AUC was 0.860,and the 95%confidence interval was 0.803-0.917.Conclusions The down-regulation of miRNA-34a-5p in cancer tissues and serum of the patients with HR-HPV-positive cervical cancer has certain reference value for the diagnosis and prognosis monitoring of cervical cancer.