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

AIM To investigate the relationship between hypoxia-inducible factor-1α(HIF-1α), prolyl 4-hydroxylase beta(P4 HB) 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 P4 HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis(GEPIA) was used to analyze the relationship between P4 HB and hypoxia-associated genes. To this end, 428 Gc tissue samples were used to analyze the expression of HIF-1α and P4 HB via immunohistochemical staining. Patient samples were classified as having weak-expression or over-expression both in terms of HIF-1α and P4 HB. Correlations between biomarkers and clinicopathological factors were analyzed to predict survival. RESULTS P4 HB demonstrated a positive correlation with hypoxiaassociated genes(P < 0.05). HIF-1α and P4 HB 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). P4 HB overexpression reflected similar results: patients with over-expression of P4 HB 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%c I: 0.52-0.88, P < 0.00; OS, 95%c I: 0.50-0.85, P < 0.00). However, P4 HB was meaningful in DFS(95%c I: 0.58-1.00, P < 0.05) but not in OS(95%c I: 0.72-1.23, P > 0.05).CONCLUSION Overexpression of HIF-1α and P4 HB is associated with poor prognosis in patients with Gc. Thus, these genes may be potential prognostic biomarker candidates in GC.

Expression of Prolyl 4-Hydroxylase Beta-Polypeptide in Non-Small Cell Lung Cancer Treated with Chinese Medicines

Objectives： To investigate the role of prolyl 4-hydroxylase beta polypeptide （P4HB） expressed in lung carcinoma and the intervention effect of Yiqi Chutan Formula （益气除痰方, YQCTF）. Methods： Lung carcinoma model was established by subcutaneously inoculating LEWIS lung carcinoma cells in C57BL/6J mice. The differential expression of P4HB protein between the YQCTF （3.0 g/kg, gavage, once daily, 21 days） group and the control group was acquired by a 2 fluorescence difference gel electrophoresis （2D-DIGE）, verified by Westem blotting and identified by matrix-assisted laser desorption ionization time of flight mass spectrometry （MALDI-TOF/＇IOF-MS）. The expression of P4HB and P4HB mRNA in cultured A549 cells from cisplatin （DDP） 1.5μg/mL group and 15% serum combined with DDP 1.5 μg/mL group were detected by cellular immunohistochemistry and reverse chain reaction, respectively. Results： The proteomics research discovered that one-third of differential proteins including P4HB were decreased in the YQCTF group （P〈0.01）. Clinical pathology and tissue microarray studies showed that P4HB expression in lung cancer tissue was stronger than adjacent tissues and normal lung epithelial （P〈0.01）. In the YQCTF and DDP combined groups, the expression of P4HB and P4HB mRNA in A549 cell were decreased significantly （P〈0.01）. Conclusion： YQCTF could inhibit the LEWIS lung carcinoma＇s growth, decrease the expression of P4HB in LEWIS lung carcinoma and A549 cells. YQCTF might take effect through regulating P4HB in endoplasmic reticulum to inhibit the incidence and growth process of lung cercinoma.