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Screening of biomarkers for prediction of response to and prognosis after chemotherapy for breast cancers

机译:筛选可预测乳腺癌化疗后反应和预后的生物标志物

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Objective: To screen the biomarkers having the ability to predict prognosis after chemotherapy for breast cancers. Methods: Three microarray data of breast cancer patients undergoing chemotherapy were collected from Gene Expression Omnibus database. After preprocessing, data in GSE41112 were analyzed using significance analysis of microarrays to screen the differentially expressed genes (DEGs). The DEGs were further analyzed by Differentially Coexpressed Genes and Links to construct a function module, the prognosis efficacy of which was verified by the other two datasets (GSE22226 and GSE58644) using Kaplan–Meier plots. The involved genes in function module were subjected to a univariate Cox regression analysis to confirm whether the expression of each prognostic gene was associated with survival. Results: A total of 511 DEGs between breast cancer patients who received chemotherapy or not were obtained, consisting of 421 upregulated and 90 downregulated genes. Using the Differentially Coexpressed Genes and Links package, 1,244 differentially coexpressed genes (DCGs) were identified, among which 36 DCGs were regulated by the transcription factor complex NFY (NFYA, NFYB, NFYC). These 39 genes constructed a gene module to classify the samples in GSE22226 and GSE58644 into three subtypes and these subtypes exhibited significantly different survival rates. Furthermore, several genes of the 39 DCGs were shown to be significantly associated with good (such as CDC20 ) and poor (such as ARID4A ) prognoses following chemotherapy. Conclusion: Our present study provided a serial of biomarkers for predicting the prognosis of chemotherapy or targets for development of alternative treatment (ie, CDC20 and ARID4A ) in breast cancer patients.
机译:目的:筛选能够预测乳腺癌化疗后预后的生物标志物。方法:从基因表达综合数据库(Gene Expression Omnibus database)收集了三例乳腺癌化疗患者的芯片数据。预处理后,使用微阵列的显着性分析对GSE41112中的数据进行分析,以筛选差异表达基因(DEG)。通过差异共表达的基因和链接进一步分析DEG,以构建功能模块,其预后效力已通过其他两个数据集(GSE22226和GSE58644)使用Kaplan-Meier图进行了验证。对功能模块中涉及的基因进行单因素Cox回归分析,以确认每个预后基因的表达是否与生存相关。结果:总共获得了511个接受或未接受化学疗法的乳腺癌患者之间的DEG,包括421个上调基因和90个下调基因。使用差异共表达基因和链接软件包,鉴定了1,244个差异共表达基因(DCG),其中36个DCG受转录因子复合物NFY(NFYA,NFYB,NFYC)调控。这39个基因构建了一个基因模块,可将GSE22226和GSE58644中的样品分为三种亚型,这些亚型的存活率差异显着。此外,显示了39个DCG的几个基因与化疗后的良好预后(如CDC20)和较差的预后(如ARID4A)显着相关。结论:我们的当前研究提供了一系列生物标志物,用于预测乳腺癌患者的化疗预后或替代治疗(例如CDC20和ARID4A)的发展目标。

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