Systematic identification of the key candidate genes in breast cancer stroma.

Background: Tumor microenvironment, in particular the stroma, plays an important role in breast cancer cell invasion and metastasis. Investigation of the molecular characteristics of breast cancer stroma may reveal targets for future study.

Methods: The transcriptome profiles of breast cancer stroma and normal breast stroma were compared to identify differentially expressed genes (DEGs). The method was analysis of GSE26910 and GSE10797 datasets. Common DEGs were identified and then analyses of enriched pathways and hub genes were performed.

Results: A total of 146 DEGs were common to GSE26910 and GSE10797. The enriched pathways were associated with "extracellular matrix (ECM) organization", "ECM-receptor interaction" and "focal adhesion". Network analysis identified six key genes, including JUN , FOS , ATF3 , STAT1 , COL1A1 and FN1 . Notably, COL1A1 and FN1 were identified for the first time as cancer stromal key genes associated with breast cancer invasion and metastasis. Oncome analysis showed that the high expression levels of COL1A1 and FN1 correlated to an advanced stage of breast cancer and poor clinical outcomes.

Conclusions: We found that several conserved tumor stromal genes might regulate breast cancer invasion through ECM remodeling. The clinical outcome analyses of COL1A1 and FN1 suggest these two genes are promising targets for future studies.