背景:MicroRNA-221-3p(miR-221-3p)通过诱导上皮-间质转化(EMT)促进乳腺癌(BC)的发展。我们的研究旨在利用生物信息学来发现miR-221-3p的可能的EMT相关靶基因(ETGs),并检查它们在乳腺癌中的作用。
方法:我们使用生物信息学技术来鉴定miR-221-3p的十个关键ETG。随后,我们对miR-221-3p和10个ETG进行了广泛的分析,包括临床意义和免疫特征。
结果:与其他亚型和邻近正常组织相比,基底样BC中miR-221-3p的表达明显更高。我们的通路分析表明,miR-221-3p可能通过MAPK信号通路通过靶向其ETG来调节EMT。在ETG中,七个核心基因(EGFR,IGF1,KDR,FGF2,KIT,FGFR1和FGF1)在BC中表现出下调。相反,ERBB2,SDC1和MMP14在BC中显示出上调,并显示出潜在的诊断价值。预后分析表明,SDC1和MMP14水平升高与预后不良相关。而KIT的表达升高与更有利的预后相关。各种免疫细胞的浸润和免疫检查点基因(ICGs)的表达与大多数ETGs和miR-221-3p呈正相关。SDC1表现出更大的肿瘤突变负荷(TMB)评分,而ERBB2,KDR,FGF2,KIT,FGFR1和FGF1显示较低的TMB评分。此外,ERBB2和KDR表达水平降低与微卫星不稳定性(MSI)评分升高相关.ETGs的表达升高与mRNA干性指数(mRNAsi)降低有关,而miR-221-3p显示相反的模式。大多数ETGs和miR-221-3p表达与药物的IC50值呈负相关。在ETG中,扩增是最重要的遗传改变,除了IGF1。
结论:结论:miR-221-3p作为基底样BC的独特指标。检查显示miR-221-3p的十个必需ETG,其中一些显示出作为诊断和预后标志物的潜力。对这十个ETGs和miR-221-3p的深入检查表明它们参与了BC的发展,强调他们作为BC患者治疗创新目标的承诺。
MicroRNA-221-3p (miR-221-3p) facilitates the advancement of breast cancer (BC) through the induction of epithelial-mesenchymal transition (EMT). Our research aimed to utilize bioinformatics to discover possible EMT-related target genes (ETGs) of miR-221-3p and examine their roles in breast cancer.
We employed bioinformatics techniques to identify ten key ETGs of miR-221-3p. Subsequently, we conducted an extensive analysis of both miR-221-3p and the ten ETGs, including clinical significance and immune characteristics.
The expression of miR-221-3p was notably higher in Basal-like BC compared to other subtypes and adjacent normal tissue. Our pathway analysis suggested that miR-221-3p might regulate EMT through the MAPK signaling pathway by targeting its ETGs. Among the ETGs, seven core genes (EGFR, IGF1, KDR, FGF2, KIT, FGFR1, and FGF1) exhibited downregulation in BC. Conversely, ERBB2, SDC1, and MMP14 showed upregulation in BC and displayed potential diagnostic value. The analysis of prognostication indicated that increased levels of SDC1 and MMP14 were correlated with an unfavorable prognosis, whereas elevated expression of KIT was associated with a more favorable prognosis. The infiltration of various immune cells and the expression of immune checkpoint genes (ICGs) exhibited positive correlations with most ETGs and miR-221-3p. SDC1 exhibited a greater tumor mutational burden (TMB) score, while ERBB2, KDR, FGF2, KIT, FGFR1, and FGF1 showed lower TMB scores. Furthermore, decreased ERBB2 and KDR expression levels were correlated with elevated microsatellite instability (MSI) scores. Elevated expression of ETGs was linked to decreased mRNA stemness indices (mRNAsi), whereas miR-221-3p displayed the opposite pattern. Most ETGs and miR-221-3p expression exhibited a negative correlation with IC50 values for drugs. Among the ETGs, amplification was the most significant genetic alteration, except for IGF1.
In conclusion, miR-221-3p acts as a unique indicator for Basal-like BC. The examination revealed ten essential ETGs of miR-221-3p, some of which show potential as diagnostic and prognostic markers. The in-depth examination of these ten ETGs and miR-221-3p indicates their participation in the development of BC, emphasizing their promise as innovative targets for therapy in BC patients.