MicroRNA Biomarkers of High-Grade Cervical Intraepithelial Neoplasia in Liquid Biopsy.
MicroRNA Biomarkers of High-Grade Cervical Intraepithelial Neoplasia in Liquid Biopsy.
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DOI：
10.1155/2021/6650966
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发表时间：
2021
影响因子：
--
通讯作者：
Marques MMC
中科院分区：
文献类型：
--
作者：
Causin RL;da Silva LS;Evangelista AF;Leal LF;Souza KCB;Pessôa-Pereira D;Matsushita GM;Reis RM;Fregnani JHTG;Marques MMC
需要新的预防策略来检测宫颈上皮内瘤变（CIN）。microRNA表达分析已经被报道为通过液体细胞学（LBC）收集获得的微创样本（如液体活检）早期检测宫颈癌（CC）的分子生物标志物。在这项研究中，我们旨在鉴定LBC宫颈前体病变中的microrna的分子特征以及可能与CC进展相关的分子途径。我们分析了31例接受阴道镜检查的女性LBC宫颈样本。将这些样本分为两组：第一组由没有CC前体病变的样本组成，考虑到对照组，称为健康女性受试者（HFS; n = 11）。第二组对应于诊断为宫颈上皮间瘤3级（CIN 3; n = 20）的妇女。我们分别使用nCounter®miRNA表达测定（NanoString Technology）和PanCancer Pathways （NanoString Technology）进行了microRNA和基因表达谱分析。利用mirDIP进行microRNA靶点预测，利用Cytoscape构建分子通路相互作用。对基因间的相关关系进行双向芯片分析和Pearson相关分析，并对差异表达的mirna进行与宫颈癌进展相关的分析。我们发现9个microrna的表达显著升高，其中2个下调（miR-381-3p和miR-4531）， 7个上调（miR-205-5p、miR-130a-3p、miR-3136-3p、miR-128-2-5p、let-7f-5p、miR-202-3p和miR-323a-5p）（倍数变化≥2，p≤0.05）。miRNA表达模式与hr-HPV感染无关。通过多元逻辑回归分析，我们确定了四种mirna （miR-205-5p, miR-130a-3p， miR-4531和miR-381-3p）可作为LBC样本中CIN 3的生物标志物。我们发现16个基因在CIN 3和HSF样本中差异表达（倍数变化≥2，p≤0.05）。我们发现miR-130a-3p与CCND1（R = - 0.52; p = 0.0029）、miR-205-5p与EGFR （R = 0.53; p = 0.0021）、miR-4531与SMAD2 （R = - 0.54; p = 0.0016）之间存在相关性。此外，我们还证实了与宫颈癌进展相关的靶点的最重要途径（经fdr校正的p < 0.001）。本研究表明，miRNA生物标志物可以区分健康子宫颈和CIN 3，并调节重要的癌变分子途径。
New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid-based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression. We analyzed 31 LBC cervical samples from women who underwent colposcopy. These samples were divided into two groups: the first group was composed of samples without precursor lesions of CC, considering the control group, referred to as healthy female subjects (HFS; n = 11). The second group corresponded to women diagnosed with cervical interepithelial neoplasia grade 3 (CIN 3; n = 20). We performed microRNA and gene expression profiling using the nCounter® miRNA Expression Assays (NanoString Technology) and PanCancer Pathways (NanoString Technology), respectively. A microRNA target prediction was performed by mirDIP, and molecular pathway interaction was constructed using Cytoscape. Bidirectional in silico analyses and Pearson's correlation were performed for associated the relation between genes, and miRNAs differentially expressed related cervical cancer progression were performed. We found that the expression of nine microRNAs was significantly higher, two were downregulated (miR-381-3p and miR-4531), and seven miRNAs were upregulated (miR-205-5p, miR-130a-3p, miR-3136-3p, miR-128-2-5p, let-7f-5p, miR-202-3p, and miR-323a-5p) in CIN 3 (fold change ≥ 2 and p ≤ 0.05). The miRNA expression patterns were independent of hr-HPV infection. We identified four miRNAs (miR-205-5p, miR-130a-3p, miR-4531, and miR-381-3p) that could be used as biomarkers for CIN 3 in LBC samples through multiple logistic regression analyses. We found 16 genes differentially expressed between CIN 3 and HSF samples (fold change ≥ 2 and p ≤ 0.05). We found the correlation between miR-130a-3p and CCND1(R = −0.52; p = 0.0029), miR-205-5p and EGFR (R = 0.53; p = 0.0021), and miR-4531 and SMAD2 (R = −0.54; p = 0.0016). In addition, we demonstrated the most significant pathways of the targets associated with cervical cancer progression (FDR-corrected p < 0.001). This study demonstrated that miRNA biomarkers may distinguish healthy cervix and CIN 3 and regulate important molecular pathways of carcinogenesis.
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影响因子：
3.4
作者：
Liu, Zhen;Mao, Lin;Hu, Xiaoxia
通讯作者：
Hu, Xiaoxia
影响因子：
6.4
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
通讯作者：
Steenbergen RDM
癌症中的microRNA生物发生途径。
DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
影响因子：
5.8
作者：
Chen AH;Qin YE;Tang WF;Tao J;Song HM;Zuo M
通讯作者：
Zuo M
影响因子：
5.6
作者：
Muinelo-Romay L;Casas-Arozamena C;Abal M
通讯作者：
Abal M