Sa1930 Genomic Signature of Subperitoneal Fibroblasts Activated in the Tumor Microenvironment Reflects Prognosis of Patients With Colon Cancer

G A A b st ra ct s CRC cell lines with high AQP9 mRNA level were more sensitive to 5-FU. Overexpression of APQ9 activated AKT phosphorylation with increased cell proliferation. Moreover, AQP9 facilitated 5-FU uptake and resulted in higher sensitivity to 5-FU. 5-FU induced cytotoxicity was relied on the NPA motif of AQP9, which is crucial for transportation function. Consistently, AQP9 overexpression facilitated tumor growth and increase tumor sensitivity to 5FU in vivo. Of clinical significance, we verified high AQP9 expression as a predictive marker for favorable therapeutic response in a cohort of 235 patients treated with 5-FU based chemotherapy. DISSCUSSION: The identification of AQP9-induced AKT activation and consequential sensitivity to 5-FU highlight the role of AQP9 in regulating chemosensitivity in CRC. On one hand, AQP9 overexpression increase cell proliferation, and rapidly proliferating cells are likely to be sensitive to therapy; on the other hand, AQP9 facilitate 5-FU transportation, hence induce cell apoptosis. Our results suggest that AQP9 might be an indicator for the necessity of 5-FU bases adjuvant chemotherapy in CRC.