Positive Phospho-Focal Adhesion Kinase in Gastric Cancer Associates With Poor Prognosis After Curative Resection

Abstract

Gastric cancer (GC) is the fifth most commonly diagnosed cancer and usually has a dismal prognosis. Our previous study highlights the contribution of focal adhesion kinase (FAK) in the tumorigenesis of diffuse gastric cancer (DGC), a subtype of GC according to Lauren classification. The prognostic value of phosphorylated FAK (pFAK) in GC remains to be explored. To explore the prognostic value of pFAK, we retrospectively collected 176 formalin-fixed paraffin-embedded (FFPE) tumor tissues from GC patients who underwent D2 gastrectomy without neoadjuvant treatment. The immunohistochemistry (IHC) staining of pFAK was performed. Survival analysis was performed by Kaplan–Meier and risk factors were evaluated by Cox regression analysis. A pFAK-based nomogram was also constructed for the prediction of overall survival (OS). We demonstrated that the prognosis of pFAK-positive patients was worse than that of the pFAK-negative patients in GC (p = 0.010; hazard ratio [HR] = 1.777, 95% CI 1.131 to 2.791; median OS, 46.6 vs. 86.3 months, respectively), and positive pFAK was also an independent risk factor for the worse prognosis of GC (p = 0.0054; HR = 1.89, 95% CI 1.21–2.96). Moreover, the nomogram based on pFAK and other independent risk factors could improve predictive accuracy for prognosis of GC. In conclusion, through analysis of a large collection of clinically annotated GC samples, we demonstrate that pFAK is a negative prognostic factor in GC, and a nomogram integrating pFAK could help predict OS for GC patients.