巴氏涂片 miR-92a-5p 和 miR-155-5p 作为鳞状上皮内宫颈癌的潜在诊断生物标志物。
Pap Smear miR-92a-5p and miR-155-5p as potential diagnostic biomarkers of squamous intraepithelial cervical cancer.
机构信息
Department of Biotechnology and Molecular Medicine, Arak University of Medical Sciences, Arak, Iran.
Department of Research and Development, Production and Research Complex, Pasteur Institute of Iran, Tehran, Iran.
出版信息
Asian Pac J Cancer Prev. 2021 Apr 1;22(4):1271-1277. doi: 10.31557/APJCP.2021.22.4.1271.
BACKGROUND
one of the female-specific diseases with a high incidence and mortality is cervical cancer. The main cause of cervical cancer is infection with Human papilloma virus (HPV). Low-grade squamous intraepithelial lesions (LSIL) and High-grade squamous intraepithelial lesions (HSIL) usually is caused by an HPV infection. Considering the role of microRNAs (miRNAs) as diagnostic biomarkers for a variety of cancers, the aim of this study was to determine miR-92a-5p and miR-155-5p expression levels in LSIL and HSIL Pap Smear samples.
METHODS
After initial bioinformatic studies, A total of 75 samples (25 samples of patients with LSIL, 25 patients with HSIL and 25 healthy individuals) were subjected to RNA extraction and cDNA synthesis. The expressions levels of confirmed miRNAs in samples of patients with LSIL, HSIL and healthy individuals were evaluated by Real time PCR analysis. To demonstration the role of predicted miRNAs as novel biomarkers in diagnosis of LSIL and HSIL, ROC curve analysis was done.
RESULTS
Bioinformatics results showed that miR-92a-5p and miR-155-5p target the HPV E6 and E7 genes. The expression levels of these miRNAs were strikingly higher in Pap smear of patients with LSIL than in the healthy individuals (35.36, P = 0.001) (62.23, P = 0.001). Similarity, expression levels of miR-92a-5p and miR-155-5p were amazingly higher in patients with HSIL than in the healthy individuals (33.62, P= 0.001) (69.07, P= 0.001). Although, the levels of miR-92a-5p (0.95, P = 0. 85) and miR-155-5p (1.11, P = 0.84) exhibited no statistical differences between patients with LSIL and HSIL. Also, ROC curve analyses verified that miR-92a-5p and miR-155-5p are specific and sensitive and may serve as new biomarkers for the early detection of cervical cancer.
CONCLUSION
These data suggest miR-92a-5p and miR-155-5p, which are upregulated in LSIL and HSIL, can be consider as predictive biomarkers for the prognosis of cervical cancer patients.
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背景
宫颈癌是一种发病率和死亡率较高的女性特有疾病。宫颈癌的主要病因是感染人乳头瘤病毒（HPV）。低度鳞状上皮内病变（LSIL）和高度鳞状上皮内病变（HSIL）通常由 HPV 感染引起。鉴于 microRNAs（miRNAs）作为多种癌症诊断生物标志物的作用，本研究旨在确定 LSIL 和 HSIL 巴氏涂片样本中 miR-92a-5p 和 miR-155-5p 的表达水平。
方法
经过初步的生物信息学研究，共对 75 例样本（25 例 LSIL 患者、25 例 HSIL 患者和 25 例健康个体）进行 RNA 提取和 cDNA 合成。通过实时 PCR 分析评估 LSIL、HSIL 患者样本中确认 miRNA 的表达水平。为了证明预测 miRNA 作为 LSIL 和 HSIL 诊断新生物标志物的作用，进行了 ROC 曲线分析。
结果
生物信息学结果表明，miR-92a-5p 和 miR-155-5p 靶向 HPV E6 和 E7 基因。LSIL 患者巴氏涂片样本中这些 miRNA 的表达水平明显高于健康个体（35.36，P=0.001）（62.23，P=0.001）。类似地，HSIL 患者样本中 miR-92a-5p 和 miR-155-5p 的表达水平明显高于健康个体（33.62，P=0.001）（69.07，P=0.001）。然而，LSIL 和 HSIL 患者之间 miR-92a-5p（0.95，P=0.85）和 miR-155-5p（1.11，P=0.84）的水平没有统计学差异。此外，ROC 曲线分析证实，miR-92a-5p 和 miR-155-5p 具有特异性和敏感性，可作为宫颈癌早期检测的新生物标志物。
结论
这些数据表明，LSIL 和 HSIL 中上调的 miR-92a-5p 和 miR-155-5p 可作为宫颈癌患者预后的预测生物标志物。
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