Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju-si, Gangwon-do, 26493, Republic of Korea.
Optipharm M&D, Inc., Wonju Eco Environmental Technology Center, Wonju-si, Gangwon-do, 26493, Republic of Korea.
BMC Cancer. 2017 Sep 21;17(1):658. doi: 10.1186/s12885-017-3642-5.
Cervical cancer is the second leading cause of death among female patients with cancer in the world. High risk human papillomavirus has causal roles in cervical cancer initiation and progression by deregulating several cellular processes. However, HPV infection is not sufficient for cervical carcinoma development. Therefore, other genetic and epigenetic factors may be involved in this complex disease, and the identification of which may lead to better diagnosis and treatment. Our aim was to analyze the expression of microRNAs in cervical cancer cases positive or negative for HPV E6/E7 mRNA, and to assess their diagnostic usefulness and relevance.
The expression of three different microRNAs (miR-9, miR-21, and miR-155) in 52 formalin-fixed paraffin-embedded (FFPE) primary cervical cancer tissue samples and 50 FFPE normal cervical tissue samples were evaluated.
MiR-9, miR-21, and miR-155 were significantly overexpressed in cervical cancer tissues compared to normal tissues (P < 0.001). MiR-21 and miR-155 expression combined with the HPV E6/E7 mRNA assay in HPV E6/E7 negative cervical cancer showed increased AUC of 0.7267 and 0.7000, respectively (P = 0.01, P = 0.04), demonstrating their potential as diagnostic tools. Moreover, miR-21 and miR-155 were predictors showing a 7 fold and 10.3 fold higher risk for HPV E6/E7 negative patients with cervical cancer (P = 0.024 and P = 0.017, respectively) while miR-155 was a predictor showing a 27.9 fold higher risk for HPV E6/E7 positive patients with cervical cancer (P < 0.0001).
There is a strong demand for additional, alternative molecular biomarkers for diagnosis and management of precancer patients. MiR-21 and miR-155 may be helpful in the prediction of both HPV positive and HPV negative cases of cervical cancer.
宫颈癌是全球女性癌症患者的第二大死亡原因。高危型人乳头瘤病毒（HPV）通过调节多种细胞过程，在宫颈癌的发生和发展中起因果作用。然而，HPV 感染不足以导致宫颈癌的发展。因此，其他遗传和表观遗传因素可能参与了这种复杂的疾病，识别这些因素可能有助于更好的诊断和治疗。我们的目的是分析 HPV E6/E7 mRNA 阳性或阴性的宫颈癌病例中 microRNAs 的表达，并评估其诊断的有效性和相关性。
我们评估了 52 例福尔马林固定石蜡包埋（FFPE）原发性宫颈癌组织样本和 50 例 FFPE 正常宫颈组织样本中三种不同 microRNAs（miR-9、miR-21 和 miR-155）的表达情况。
与正常组织相比，宫颈癌组织中 miR-9、miR-21 和 miR-155 的表达显著上调（P<0.001）。miR-21 和 miR-155 的表达与 HPV E6/E7 mRNA 检测联合应用于 HPV E6/E7 阴性的宫颈癌患者时，AUC 分别增加至 0.7267 和 0.7000（P=0.01，P=0.04），表明它们具有作为诊断工具的潜力。此外，miR-21 和 miR-155 是预测因子，可使 HPV E6/E7 阴性的宫颈癌患者的风险分别增加 7 倍和 10.3 倍（P=0.024 和 P=0.017），而 miR-155 是预测因子，可使 HPV E6/E7 阳性的宫颈癌患者的风险增加 27.9 倍（P<0.0001）。
对于诊断和管理癌前患者，强烈需要额外的替代分子生物标志物。miR-21 和 miR-155 可能有助于预测 HPV 阳性和 HPV 阴性的宫颈癌病例。
