The differential expression of vascular endothelial growth inhibitor isoforms, VEGI251, VEGI174 and VEGI192 in human clear-cell renal cell carcinoma.

UNLABELLED: Vascular endothelial growth inhibitor (VEGI) is a recently identified antiangiogenic cytokine that belongs to the tumour necrosis factor (TNF) superfamily, and may be essential for many physiological and pathological processes. However, the expression of VEGI and in particular its isoforms, VEGI251, VEGI192 and VEGI174, in clear-cell renal cell carcinoma (CCRCC) remain unknown. In the current study, we investigated the expression of the three isoforms of VEGI in CCRCC. The expression of VEGI was examined in paired human normal renal and CCRCC specimens (n=73). The transcripts of the three isoforms of VEGI were all detected in human renal normal and tumour tissues. Levels of VEGI174 and VEGI192 transcripts in normal renal specimens were higher than those in CCRCC (p=0.021 and p=0.038, respectively). Levels of VEGI251 were similar in normal and tumour specimens (p=0.67). The numbers of VEGI174 and VEGI192 transcripts in T1a+T1b tumours were higher than those in T2+T3 tumours (p=0.006 and p=0.018, respectively). Moreover, VEGI192 transcript levels were negatively correlated with pathological nuclear grade (r=-0.216, p=0.022). In immunohistochemical staining, VEGI192 staining in normal and CCRCC tissues differed significantly (100% vs. 39.7%, p<0.0001). VEGI192 staining intensity was also negatively correlated with pathological nuclear grade (r=-0.781, p=0.002).

CONCLUSION: Transcripts of VEGI isoforms were detectable in normal and tumour renal tissues. VEGI192 and VEGI174 expressions markedly decreased in CCRCC and are linked to pathological grade and stage. VEGI192 and VEGI174 are more likely to be putative tumour suppressive factors and a potential therapeutic target in CCRCC.