Expression of Karyopherin Alpha 2 and Karyopherin Beta 1 Correlate with Poor Prognosis in Gastric Cancer

INTRODUCTION: Karyopherin alpha 2 (KPNA2) and karyopherin beta 1 (KPNB1) constitute nuclear transport protein complexes involved in nuclear import and are significant in tumor progression. Although high KPNA2 expression was associated with poor prognosis in solid tumors, the relationship between KPNA2 and KPNB1 expression and their prognostic role in gastric cancer (GC) remains unclear. METHODS: Immunohistochemistry was used to correlate the expression of KPNA2 and KPNB1 with various features, including clinicopathological characteristics in 130 patients with GC and survival in 94 patients with invasive lesions extending to the submucosa or deeper. RESULTS: High expression of KPNA2 and KPNB1 was found in 25% and 36% of the patients, respectively. Both were significantly related to tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and Ki-67 expression. KPNA2 expression was significantly related to that of KPNB1 (p < 0.001). Patients with high KPNB1 expression had poorer prognosis than those with low expression (p = 0.027), as was also observed in case of KPNA2 (p < 0.001). Patients with high expression of both KPNA2 and KPNB1 accounted for 18% and had a poorer prognosis than those with high expression of either and those with low expression of both (p = 0.001). Multivariate analysis revealed that high expression of both KPNA2 and KPNB1 was an independent prognostic factor in patients with GC (hazard ratio, 3.46; 95% confidence interval, 1.64–2.73, p = 0.001). CONCLUSION: KPNA2 expression was correlated with KPNB1 expression, and high co-expression of KPNA2 and KPNB1 may represent a strong prognostic biomarker in GC.