Targeting the tumor stroma: integrative analysis reveal GATA2 and TORYAIP1 as novel prognostic targets in breast and ovarian cancer

Authors: ÖMER FARUK ERCEYLAN, AYŞE SAVAŞ, ESRA GÖV

Abstract: Tumor stroma interaction is known to take a crucial role in cancer growth and progression. In the present study, it was performed gene expression analysis of stroma samples with ovarian and breast cancer through an integrative analysis framework to identify common critical biomolecules at multiomics levels. Gene expression datasets were statistically analyzed to identify common differentially expressed genes (DEGs) by comparing tumor stroma and normal stroma samples. The integrative analyses of DEGs indicated that there were 59 common core genes, which might be feasible to be potential marks for cancer stroma targeted strategies. Reporter molecules (i.e. receptor, transcription factors and miRNAs) were determined through a statistical test employing the hypergeometric probability density function. Afterward, the tumor microenvironment protein-protein interaction and the generic network were reconstructed by using identified reporter molecules and common core DEGs. Through a systems medicine approach, it was determined that hub biomolecules, AR, GATA2, miR-124, TOR1AIP1, ESR1, EGFR, STAT1, miR-192, GATA3, COL1A1, in tumor microenvironment generic network. These molecules were also identified as prognostic signatures in breast and ovarian tumor samples via survival analysis. According to literature searching, GATA2 and TORYAIP1 might represent potential biomarkers and candidate drug targets for the stroma targeted cancer therapy applications.

Keywords: Gene expression, cancer stroma, biomarkers, network medicine

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