Feature genes in metastatic breast cancer identified by MetaDE and SVM classifier methods

Abstract

The aim of the present study was to investigate the feature genes in metastatic breast cancer samples. A total of 5 expression profiles of metastatic breast cancer samples were downloaded from the Gene Expression Omnibus database, which were then analyzed using the MetaQC and MetaDE packages in R language. The feature genes between metastasis and non-metastasis samples were screened under the threshold of P<0.05. Based on the protein-protein interactions (PPIs) in the Biological General Repository for Interaction Datasets, Human Protein Reference Database and Biomolecular Interaction Network Database, the PPI network of the feature genes was constructed. The feature genes identified by topological characteristics were then used for support vector machine (SVM) classifier training and verification. The accuracy of the SVM classifier was then evaluated using another independent dataset from The Cancer Genome Atlas database. Finally, function and pathway enrichment analyses for genes in the SVM classifier were performed. A total of 541 feature genes were identified between metastatic and non-metastatic samples. The top 10 genes with the highest betweenness centrality values in the PPI network of feature genes were Nuclear RNA Export Factor 1, cyclin-dependent kinase 2 (CDK2), myelocytomatosis proto-oncogene protein (MYC), Cullin 5, SHC Adaptor Protein 1, Clathrin heavy chain, Nucleolin, WD repeat domain 1, proteasome 26S subunit non-ATPase 2 and telomeric repeat binding factor 2. The cyclin-dependent kinase inhibitor 1A (CDKN1A), E2F transcription factor 1 (E2F1), and MYC interacted with CDK2. The SVM classifier constructed by the top 30 feature genes was able to distinguish metastatic samples from non-metastatic samples [correct rate, specificity, positive predictive value and negative predictive value >0.89; sensitivity >0.84; area under the receiver operating characteristic curve (AUROC) >0.96]. The verification of the SVM classifier in an independent dataset (35 metastatic samples and 143 non-metastatic samples) revealed an accuracy of 94.38% and AUROC of 0.958. Cell cycle associated functions and pathways were the most significant terms of the 30 feature genes. A SVM classifier was constructed to assess the possibility of breast cancer metastasis, which presented high accuracy in several independent datasets. CDK2, CDKN1A, E2F1 and MYC were indicated as the potential feature genes in metastatic breast cancer.

Signature microRNAs and long noncoding RNAs in laryngeal cancer recurrence identified using a competing endogenous RNA network

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Lactate Activates the E2F Pathway to Promote Cell Motility by Up-Regulating Microtubule Modulating Genes

“…Functional studies of E2F proteins as transcription factors clearly defined their roles in cell cycle control [22]. Furthermore, E2F target genes involved in metastasis or angiogenesis were also reported in breast cancer and melanoma [23,24,25]. However, roles of E2Fs in tumor metastasis have not been reported yet.…”

“…However, recent reports indicated a possibility that E2Fs might also have roles in cell motility regulation. Thus, E2F target genes were shown to regulate tumor metastasis in breast cancer and nasopharyngeal cancer [25,39]. In addition, E2F2 pathway was associated with relapse-free survival time of breast cancer patients [40].…”

Gene expression signatures predict response to therapy with growth hormone

“…The hierarchy of overlapping modules of genes was identified in each network using the network topology parameter of “centrality” (Supplemental Table S4) . Network centrality is measurement that is known to be related to gene function within networks; the more central a gene is, the more capable it is of influencing other genes within the network ( 20 ).…”