Correlation and expression analysis of hypoxia-inducible factor 1α, glucose transporter 1 and lactate dehydrogenase 5 in human gastric cancer

The development and identification of novel potential targeting sites for intervention therapy are essential in the search for improved treatment methods for gastric cancer (GC). Previously, it has been reported that hypoxia inducible factor-1 alpha (HIF-1 alpha) is a potential target gene involved in the endogenous hypoxic response and bioenergetic metabolism of GC cells. In the present study, with the assumption of a close interplay among HIF-1 alpha, glucose transporter 1 (GLUT1) and lactate dehydrogenase-5 (LDH-5), 85 patients with GC were recruited and the protein and gene expression levels of HIF-1 alpha, GLUT1 and LDH-5 in tumor tissues were evaluated in order to assess clinical correlations and co-expression patterns, using Immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that the protein and gene expression levels of HIF-1 alpha were significantly associated with the depth of invasion, nodal metastasis, clinical stage, differentiation and distant metastasis. Consistent with the protein expression results, the mRNA expression levels of the genes coding for GLUT1 and LDH-5 were clearly associated with tumor size, depth of invasion, distant metastasis, clinical stage and differentiation. Correlation analysis of HIF-1 alpha with GLUT1 and LDH-5 at the protein and mRNA expression levels in gastric carcinoma indicated that HIF-1 alpha expression was positively correlated with the expression of GLUT1 (P<0.01, r=0.765 for mRNA expression; P<0.01, r=0.697 for protein expression) and LDH-5 (P<0.01, r=0.892 for mRNA expression; P<0.01, r=0.783 for protein expression) at the mRNA and protein levels. Therefore, it may be concluded that HIF-1 alpha, GLUT1 and LDH-5 are potential target genes involved in the endogenous tumor response to hypoxia and the inhibition of tumor energy metabolism, highlighting a novel therapeutic target for GC.