Differentially Expressed Nuclear Encoded Mitochondrial Genes In Breast Cancer Epithelial And Stromal Cells And Functional Module Analysis

It has been reported that tumor microenvironment,which can affect functions of tumor epithelial and stromal cells.It is well known that the mitochondria are the"powerhouse" of cells.In this paper,we infer that nuclear encoded mitochondrial genes,which may be involved in cancer growth and metastasis,are differentially expressed in the breast cancer epithelial cell and stromal cells.The gene expression profiles were obtained from the GEO website of NCBI with the accession number GSE10797,then we chose the MitoCarta database,and we finally obtained 714 human nuclear encoded mitochondrial genes by the official gene symbol.We used Wilcoxon test to identify the differentially expressed nuclear encoded mitochondrial genes and annotate those genes by Gene Ontology(GO).To identify enriched Gene Ontology(GO)biological process categories and KEGG pathways,we chose the DAVID database to analysis those genes.We found that the mitochondrial membrane respiratory chain Complex I and Complex IV were defect in the breast cancer epithelial and stromal cells.We also found that the TCA cycle was uninhibited and related enzymes were actived.Our result is same as Warburg effect.Besides that,we found that transport related genes were significant in the breast cancer epithelial cells,especially for SLC25A16 gene which is involved in TCA cycle.We also found that LDHB gene,biomarker of triple-negative breast cancer,was down-regulated.Eichner L J.et al reported that this gene is relevant to ESRRA and ESRRG,so we detect 7 estrogen-receptor related genes(ESR1,ESR2,ESRPI,ESRP2,ESRRA,ESRRB and ESRRG)in breast cancer epithelial cells and stromal cells.However,our result were different to the result of Eichner L J.et al,ESRRA gene was up-regulated in the epithelial cells and ESRRG was no significant change in both epithelial cells and stromal cells.Finally,we got 5 up-regulated genes and 20 down-regulated genes both in epithelial and stromal cells.Identification the functional modules of the five common up-regulated genes centered network;we retrieved the network from STRING database and integrate the network with gene expression profiles.The FH centered network which contained 198 nodes and 957 edges could be analyses.We represented an improved simulated annealing algorithm SANetWalker to detect the functional module,and we obtained the highest confidence functional module with 40 nodes and 107 edges.We used DAVID to analysis enriched Gene Ontology(GO)biological process categories and KEGG pathways,we thought the N-element metabolism is crucial to breast cancer growth and metastasis.