Dysregulation of EGFR pathway in EphA2 cell subpopulation significantly associates with poor prognosis in colorectal cancer

摘要: Purpose: EphA2 receptor is involved in multiple cross-talks with other cellular networks including EGFR, FAK and VEGF pathways, which it collaborates to stimulate cell migration, invasion metastasis. Colorectal cancer (CRC) overexpression has also been correlated stem-like properties of cells tumor malignancy. We investigated the molecular crosstalk microRNAs modulation EGFR pathways. We explored role EphA2/EGFR pathway mediators as prognostic factors or predictors cetuximab benefit CRC patients. Experimental Design: Gene expression analysis was performed EphA2high isolated from AOM/DSS murine model by FACS-assisted procedures. Six independent cohorts patients were stratified determine potential a signature its effect on treatment response. Results: identified gene pattern (EphA2, Efna1, Ptpn12, Atf2) reflecting activation pathways coherent dysregulation mir-26b mir-200a. Such showed significance stage I-III patients, both univariate multivariate analysis. In IV WT KRAS, EphA2/Efna1/EGFR status significantly associated poor response treatment. Furthermore, combined relative resistance, independently KRAS mutation status. Conclusions: These results suggest that genes, linked possible control mir-200a mir-26b, could be proposed novel biomarkers. Moreover, mechanism resistance alternative mutations.