Arg388 Is Correlated with Poor Survival in Resected Colon Cancer Promoting Epithelial to Mesenchymal Transition.

PURPOSE

Fibroblast growth factor receptor 4 () plays an important role in cancer progression during tumor proliferation, invasion, and metastasis. This study evaluated the prognostic role of polymorphism in patients with resected colon cancer, including the underlying mechanism.

MATERIALS AND METHODS

polymorphism was characterized in patientswho received curative resection for stage III colon cancer. -dependent signal pathways involving cell proliferation, invasion, and migration according to genotypes were also evaluated in transfected colon cancer cell lines.

RESULTS

Among a total of 273 patients, the GG of showed significantly better overall survival than the AG or AA, regardless of adjuvant treatment. In the group of AG or AA, combination of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) resulted in better survival than fluorouracil/leucovorin or no adjuvant chemotherapy. However, in GG, there was no difference among treatment regimens. Using multivariate analyses, the Arg388 carriers, together with age, N stage, poor differentiation, absence of a lymphocyte response, and no adjuvant chemotherapy, had a significantly worse OS than patients with the Gly388 allele. In transfected colon cancer cells, overexpression of Arg388 significantly increased cell proliferation and changes in epithelial to mesenchymal transition markers compared with cells overexpressing the Gly388 allele.

CONCLUSION

The Arg388 allele of may be a biomarker and a candidate target for adjuvant treatment of patients with resected colon cancer.