Microarray and pattern miner analysis of AXL and VIM gene networks in MDA-MB-231 cells

MDA-MB-231 cells represent malignant triple-negative breast cancer, which overexpress epidermal growth factor receptor (EGFR) and two genes (AXL and VIM) associated with poor prognosis. The present study aimed to identify novel therapeutic targets and elucidate the functional networks for the AXL and VIM genes in MDA-MB-231 cells. We identified 71 genes upregulated in MDA-MB-231 vs. MCF7 cells using BRB-Array tool to re-analyse microarray data from six GEO datasets. Gene ontology and STRING analysis showed that 43/71 genes upregulated in MDA-MB-231 compared with MCF7 cells, regulate cell survival and migration. Another 19 novel genes regulate migration, metastases, senescence, autophagy and chemoresistance. The Pattern Miner systems biology tool uses specific genes as inputs or baits' to identify outputs from the NCI-60 database. Using five genes regulating cancer cell migration (AXL, VIM, EGFR, CAPN2, and COL4A1) as input baits', we used pattern miner to identify statistically significant, co-expressed genes from the list of 71 genes upregulated in MDA-MB-231 compared with MCF7 cells. Outputs were subsets of the 71 genes, which showed significant co-expression with one or more of the five input genes. These outputs were used to develop functional networks for AXL and VIM. Analysis of these networks verified known properties of AXL and VIM, and suggested novel functions for these two genes. Thus, genes in the AXL network promote migration, metastasis and chemoresistance, whereas the VIM gene network regulates novel tumorigenic processes, such as lipogenesis, senescence and autophagy. Notably, these two networks contain 12 genes not reported for TNBC.