Prognostic value of hypoxia-inducible factor-1 alpha and prolyl 4-hydroxylase beta polypeptide overexpression in gastric cancer.

ABSTRACT

AIM: To investigate the relationship between hypoxia-inducible factor-1α (HIF-1α), prolyl 4-hydroxylase beta (P4HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer (GC). METHODS: Hypoxia is a critical factor that shapes the GC microenvironment. In previous reports, we have demonstrated that P4HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis (GEPIA) was used to analyze the relationship between P4HB and hypoxia-associated genes. To this end, 428 GC tissue samples were used to analyze the expression of HIF-1α and P4HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS: P4HB demonstrated a positive correlation with hypoxia-associated genes (P < 0.05). HIF-1α and P4HB overexpression have a significant correlation with TNM staging (χ2 = 23.32, P = 0.00; χ2 = 65.64, P = 0.00) and peritoneum cavity metastasis (χ2 = 12.67, P = 0.00; χ2 = 39.29, P = 0.00). In univariate analysis, patients with a high HIF-1α expression trend had a shorter disease-free survival (DFS 44.80 mo vs 22.06 mo) and overall survival (OS 49.58 mo vs 39.92 mo). P4HB overexpression reflected similar results: patients with over-expression of P4HB had a shorter survival time than those with weak-expression (DFS 48.03 mo vs 29.64 mo, OS 52.48 mo vs 36.87 mo). Furthermore, HIF-1α is also a clinicopathological predictor of dismal prognosis according to multivariate analysis (DFS, 95%CI 0.52-0.88, P < 0.00; OS, 95%CI 0.50-0.85, P < 0.00). However, P4HB was meaningful in DFS (95%CI 0.58-1.00, P < 0.05) but not in OS (95%CI 0.72-1.23, P > 0.05). CONCLUSION: Overexpression of HIF-1α and P4HB is associated with poor prognosis in patients with GC. Thus, these genes may be potential prognostic biomarker candidates in GC.