The Correlation Between Nedd4l And Hif-1 Alpha Levels As A Gastric Cancer Prognostic Marker

NEDD4L (neural precursor cell expressed developmentally down-regulated 4-like) protein is a member of ubiquitin ligases Nedd4 family. Although studies have shown that Nedd4L may act as a tumor suppressor in various cancers, including gastric cancer (GC), its clinical significance and the diagnostic value in GC is not well defined. HIF-1 alpha (hypoxia inducible factor family of transcription factors) is actively involved in the metabolism of many tumors, although the relationship between its expression levels and clinical significance in GC still need to be established. In this study, the level of HIF-1 alpha and NEDD4L mRNA and protein in 25 freshly frozen GC-and matched normal-tissues were determined by western blot and quantitative PCR (qPCR). Additionally, immunohistochemistry assay was performed to measure the protein level of NEDD4L and HIF-1 alpha in 124 GC and 25 normal control tissues. We observed that the NEDD4L mRNA and protein levels decreased significantly (P < 0.001) in GC tissues, while that of HIF-1 alpha increased (P < 0.001), and they both were associated with a poor prognosis, as was the case in patients with lower NEDD4L and higher HIF-1 alpha expression (P < 0.001). On correlation analysis, a significantly negative relationship (r = 0.288, P < 0.01) was revealed between NEDD4L and HIF-1 alpha expressions. Multivariate analysis revealed that co-expression of NEDD4L (P < 0.05) and HIF-1 alpha (P < 0.001) were independent predictors of GC prognosis. Thus, the correlation of NEDD4L and HIF-1 alpha levels may act as a prognostic marker of GC.