Centre for Bioinformatics, School of Life Sciences, Pondicherry University, Pondicherry, India.
J Cell Physiol. 2019 Jul;234(7):11768-11779. doi: 10.1002/jcp.27839. Epub 2018 Nov 29.
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor clinical outcomes and lack of approved targeted therapy. Dysregulated microRNAs (miRNAs) have been considered a promising biomarker, which plays an important role in the tumorigenesis of human cancer. Due to the increase in miRNA profiling datasets of TNBC, a proper analysis is required for studying. Therefore, this study used meta-analysis to amalgamate ten miRNA profiling studies of TNBC. By the robust rank aggregation method, metasignatures of six miRNAs (4 upregulated: hsa-miR-135b-5p, hsa-miR-18a-5p, hsa-miR-9-5p and hsa-miR-522-3p; 2 downregulated: hsa-miR-190b and hsa-miR-449a) were obtained. The gene ontology analysis revealed that target genes regulated by miRNAs were associated with processes like the regulation of transcription, DNA dependent, and signal transduction. Also, it is noted from the pathway analysis that signaling and cancer pathways were associated with the progression of TNBC. A Naïve Bayes-based classifier built with miRNA signatures discriminates TNBC and non-TNBC samples in test data set with high diagnostic sensitivity and specificity. From the analysis carried out by the study, it is suggested that the identified miRNAs are of great importance in improving the diagnostics and therapeutics for TNBC.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌亚型，临床结局较差，缺乏批准的靶向治疗方法。失调的 microRNAs（miRNAs）被认为是一种很有前途的生物标志物，在人类癌症的发生中发挥着重要作用。由于 TNBC 的 miRNA 图谱数据集的增加，需要进行适当的分析来进行研究。因此，本研究使用荟萃分析合并了 10 项 TNBC 的 miRNA 图谱研究。通过稳健的秩聚合方法，获得了 6 个 miRNA（4 个上调：hsa-miR-135b-5p、hsa-miR-18a-5p、hsa-miR-9-5p 和 hsa-miR-522-3p；2 个下调：hsa-miR-190b 和 hsa-miR-449a）的 metasignatures。基因本体论分析表明，miRNAs 调控的靶基因与转录调控、DNA 依赖性和信号转导等过程有关。此外，通路分析还指出，信号和癌症通路与 TNBC 的进展有关。基于朴素贝叶斯的分类器，使用 miRNA 特征可以在测试数据集区分 TNBC 和非 TNBC 样本，具有较高的诊断敏感性和特异性。从该研究进行的分析中，可以看出鉴定出的 miRNA 对提高 TNBC 的诊断和治疗具有重要意义。
