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

Abstract

AIMTo 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).METHODSHypoxia 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.RESULTSP4HB 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).CONCLUSIONOverexpression 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.

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“…Although traditional treatment strategies have improved, the 5-year survival rate is still low. 15 Therefore, it is critical that GC is diagnosed early, and finding a suitable plasma molecular biomarker may be an effective method to achieve this goal. Several studies have demonstrated the feasibility of using circulating lncRNAs as biomarkers for tumor diagnosis; however, numerous preanalytical and analytical aspects, such as sample choice, extraction method, and donor-related factors, may affect the accuracy of circulating lncRNA determination.…”

<p>To Develop and Validate the Combination of RNA Methylation Regulators for the Prognosis of Patients with Gastric Cancer</p>

“…The steps of immunohistochemistry were performed as formerly described. 10 The ultimate immunoreactivity scores (IRS) were calculated consistent with the scores of the ratio of positive dyed cells, as previously described. 10 …”

lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p

“…In experimental models, the activation of this pathway has been shown to promote the progression of gastric cancer (53). HIF-1 can up-regulate EMT-related transcription factors and is closely related to the prognosis of gastric cancer (54). Those results led us to speculate on the key role of DLEU2 in tumor hypoxia.…”