Genome-wide microRNA analysis of HPV-positive self-samples yields novel triage markers for early detection of cervical cancer.
Genome-wide microRNA analysis of HPV-positive self-samples yields novel triage markers for early detection of cervical cancer.
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DOI：
10.1002/ijc.31855
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发表时间：
2019-01-15
影响因子：
6.4
通讯作者：
Steenbergen RDM
中科院分区：
文献类型：
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作者：
Snoek BC;Verlaat W;Babion I;Novianti PW;van de Wiel MA;Wilting SM;van Trommel NE;Bleeker MCG;Massuger LFAG;Melchers WJG;Sie D;Heideman DAM;Snijders PJF;Meijer CJLM;Steenbergen RDM
为HPV检测提供自我采样通过增加人口覆盖率提高了当前宫颈筛查计划的有效性。需要直接适用于自身样本的分子标记物来对HPV阳性女性进行宫颈癌风险分层（所谓的分流），并避免过度转诊和过度治疗。失调的microRNAs（miRNAs）与宫颈癌的发生有关，是潜在的分类标志物。然而，目前尚不清楚是否在自身样本中反映了失调的miRNA表达。我们的研究是第一个在HPV阳性自身样本中建立全基因组miRNA谱的研究，以鉴定可以预测自身样本中CIN 3和宫颈癌存在的miRNA。进行小RNA测序（sRNA-Seq）以确定74例HPV阳性的宫颈癌前病变（CIN 3）女性自身样本的全基因组miRNA表达谱。用于CIN 3检测的最佳miRNA标记物组通过GRridge确定，GRridge是逻辑回归的惩罚方法。通过qPCR在191个独立的HPV阳性自身样本中验证了6种miRNA。sRNA-Seq数据的分类产生了9-miRNA标记物组，其CIN 3检测的组合曲线下面积（AUC）为0.89。通过qPCR验证，CIN 3+检测的组合AUC为0.78。我们的研究表明，在HPV阳性的自身样本中，可以通过sRNA-Seq检测到与CIN 3和宫颈癌发展相关的miRNA表达失调。通过qPCR的验证表明，miRNA表达分析为CIN 3和宫颈癌检测提供了一种适用于自身样本的有前途的新型分子分类策略。 有什么新消息吗？ microRNAs（miRNAs）被怀疑在宫颈癌的发展中发挥作用。它们也是鉴定人乳头瘤病毒（HPV）感染的女性有宫颈癌风险的潜在标志物。在这里，使用来自患有和不患有宫颈癌前病变（CIN 3）的女性的HPV阳性自身样本的小RNA测序，作者鉴定了由多个miRNA组成的miRNA特征，其强烈预测CIN 3。通过qPCR验证该特征揭示了CIN 3+检测的良好临床性能。研究结果表明，miRNA分析是宫颈癌筛查中HPV阳性自身样本中CIN 3+预测的有效手段。
Offering self‐sampling for HPV testing improves the effectiveness of current cervical screening programs by increasing population coverage. Molecular markers directly applicable on self‐samples are needed to stratify HPV‐positive women at risk of cervical cancer (so‐called triage) and to avoid over‐referral and overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the development of cervical cancer, and represent potential triage markers. However, it is unknown whether deregulated miRNA expression is reflected in self‐samples. Our study is the first to establish genome‐wide miRNA profiles in HPV‐positive self‐samples to identify miRNAs that can predict the presence of CIN3 and cervical cancer in self‐samples. Small RNA sequencing (sRNA‐Seq) was conducted to determine genome‐wide miRNA expression profiles in 74 HPV‐positive self‐samples of women with and without cervical precancer (CIN3). The optimal miRNA marker panel for CIN3 detection was determined by GRridge, a penalized method on logistic regression. Six miRNAs were validated by qPCR in 191 independent HPV‐positive self‐samples. Classification of sRNA‐Seq data yielded a 9‐miRNA marker panel with a combined area under the curve (AUC) of 0.89 for CIN3 detection. Validation by qPCR resulted in a combined AUC of 0.78 for CIN3+ detection. Our study shows that deregulated miRNA expression associated with CIN3 and cervical cancer development can be detected by sRNA‐Seq in HPV‐positive self‐samples. Validation by qPCR indicates that miRNA expression analysis offers a promising novel molecular triage strategy for CIN3 and cervical cancer detection applicable to self‐samples. What's new? MicroRNAs (miRNAs) are suspected of playing a role in cervical cancer development. They are also potential markers for the identification of human papillomavirus (HPV)‐infected women who are at risk of cervical cancer. Here, using small RNA sequencing of HPV‐positive self‐samples from women with and without cervical precancer (CIN3), the authors identify a miRNA signature consisting of multiple miRNAs that is strongly predictive of CIN3. Validation of this signature by qPCR revealed a good clinical performance for CIN3+ detection. The findings suggest that miRNA analysis is an effective means of CIN3+ prediction in HPV‐positive self‐samples obtained for cervical cancer screening.
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影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
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作者：
Koppers-Lalic D;Hackenberg M;de Menezes R;Misovic B;Wachalska M;Geldof A;Zini N;de Reijke T;Wurdinger T;Vis A;van Moorselaar J;Pegtel M;Bijnsdorp I
通讯作者：
Bijnsdorp I
影响因子：
4.3
作者：
Magee, Rogan;Telonis, Aristeidis G.;Londin, Eric
通讯作者：
Londin, Eric
影响因子：
9.4
作者：
Hesselink, A. T.;Berkhof, J.;Heideman, D. A. M.
通讯作者：
Heideman, D. A. M.
microRNAs 差异调节介导人乳头瘤病毒 (HPV) 诱导的宫颈上皮内瘤变 (CIN) 的进展
影响因子：
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作者：
Mo W;Tong C;Zhang Y;Lu H
通讯作者：
Lu H