Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, 210008, China.
Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China.
BMC Cancer. 2019 Oct 23;19(1):986. doi: 10.1186/s12885-019-6066-6.
To examine differences in the plasma levels of miRNA-21, - 214, -34a, and -200a in patients with persistent high-risk human papillomavirus (hr-HPV) infection or with cervical lesions of different grades.
Venous blood was collected from 232 individuals to measure the plasma expression levels of miRNA-21, - 214, -34a, and -200a. The subjects included normal controls and patients with persistent hr-HPV infection, CIN1, CIN2, CIN3, or cervical cancer (n = 42, 31, 19, 54, 71, and 15 patients, respectively). Cervical conization specimens were collected from all the women. To ensure the accuracy of histopathology, three consecutive tissue sections with an identical diagnosis were selected, and dissection samples were taken from them for miRNA detection. Eligible cases met the inclusion criteria based on sample observation using the middle slice of sandwich tissue sections from the pathological tissue in accordance with the diagnosis of CIN1, CIN2 and CIN3 in 8, 29, and 26 cases, respectively. The miRNA-21, - 214, -34a, and -200a expression levels in the paraffin-embedded tissue samples were determined. The percentage of patients with a CIN2+ diagnosis at 30-49 years old was significantly different from that of those diagnosed with CIN1. The incidence of CIN2+ patients exposed to passive smoking was significantly different from that of CIN1- patients. The percentage of CIN2+ patients with three pregnancies was significantly different from that of those with CIN1, and the percentage of CIN2+ subjects with ≥4 pregnancies was significantly different from that of CIN1- patients. The number of CIN2+ patients with two or more induced abortions was significantly different from that of patients with CIN1. The percentage of CIN2+ patients who underwent a caesarean section was significantly different from that of patients with CIN. The percentage of CIN2+ patients with first-degree relatives with cancer was significantly different from that of those with CIN1. Among CIN2+ patients, the percentage with a first sexual encounter at ≤20 years old was significantly different from that of those with CIN1. The percentage of CIN2+ patients with ≥2 sexual partners was significantly different from that of CIN1- patients.
The plasma miRNA-214, -34a, and -200a expression levels were decreased in patients with more severe cervical lesions. Plasma miRNA levels in CIN1- patients were significantly different from those in CIN2+ patients. The kappa values for miRNA-21, - 214, -34a and -200a in tissue versus plasma were 0.7122, 0.9998, 0.8986 and 0.7458, respectively. The sensitivity of each biomarker for detecting CIN2 was calculated, and ROC curves of the four miRNA biomarkers were drawn. The AUC of the four plasma miRNAs was greater than 0.5, with the AUC of miRNA-21 being the largest at 0.703. The plasma miRNA expression levels exhibited at least one tie between CIN1 and CIN2. The AUCs for miRNA-21, -34a, -200a and - 214 were 0.613, 0.508, 0.615 and 0.505, respectively.
Changes in plasma miRNA-21, - 214, -34a and -200a levels were associated with cervical lesion severity. The plasma miRNA levels in CIN1- subjects were significantly different from those in CIN2+ subjects. This analysis may help in detection of high-grade cervical lesions.
检测持续性高危型人乳头瘤病毒（hr-HPV）感染或不同分级宫颈病变患者血浆中 miRNA-21、-214、-34a 和 -200a 的水平差异。
采集 232 例个体的静脉血，测量 miRNA-21、-214、-34a 和 -200a 的血浆表达水平。研究对象包括正常对照者和持续性 hr-HPV 感染、CIN1、CIN2、CIN3 或宫颈癌患者（分别为 42、31、19、54、71 和 15 例患者）。所有女性均采集宫颈锥切标本。为确保组织病理学检查的准确性，选择了诊断相同的连续 3 个组织切片，并从这些切片中采集样本进行 miRNA 检测。符合条件的病例根据 8、29 和 26 例 CIN1、CIN2 和 CIN3 病理组织中中间切片的组织观察结果，符合纳入标准。检测石蜡包埋组织样本中 miRNA-21、-214、-34a 和 -200a 的表达水平。30-49 岁 CIN2+患者比例与 CIN1 患者显著不同。被动吸烟暴露的 CIN2+患者发生率与 CIN1-患者显著不同。有 3 次妊娠的 CIN2+患者比例与 CIN1 患者显著不同，有≥4 次妊娠的 CIN2+患者比例与 CIN1-患者显著不同。有 2 次或更多次人工流产的 CIN2+患者比例与 CIN1 患者显著不同。行剖宫产的 CIN2+患者比例与 CIN 患者显著不同。有一级亲属患癌症的 CIN2+患者比例与 CIN1 患者显著不同。在 CIN2+患者中，首次性行为发生在≤20 岁的比例与 CIN1 患者显著不同。有≥2 个性伴侣的 CIN2+患者比例与 CIN1-患者显著不同。
宫颈病变越严重，血浆 miRNA-214、-34a 和 -200a 表达水平越低。CIN1-患者的血浆 miRNA 水平与 CIN2+患者显著不同。miRNA-21、-214、-34a 和 -200a 在组织与血浆中的 kappa 值分别为 0.7122、0.9998、0.8986 和 0.7458。计算了每个生物标志物对检测 CIN2 的敏感性，并绘制了 4 种 miRNA 生物标志物的 ROC 曲线。4 种血浆 miRNA 的 AUC 均大于 0.5，miRNA-21 的 AUC 最大，为 0.703。miRNA-21、-34a、-200a 和 -214 的 AUC 分别为 0.613、0.508、0.615 和 0.505。
血浆 miRNA-21、-214、-34a 和 -200a 水平的变化与宫颈病变严重程度有关。CIN1-患者的血浆 miRNA 水平与 CIN2+患者显著不同。该分析可能有助于检测高级别宫颈病变。
