Increased caveolin-1 expression associated with prolonged overall survival rate in hepatocellular carcinoma

Aims: Recent study indicates that the binding of caveolin-1 (CAV1), the essential constituent of caveolae, to endothelial nitric oxide synthase (eNOS) prevents nitric oxide (NO) production in cirrhotic human liver. However, their interplay in hepatocellular carcinoma (HCC) remains undetermined. Methods: Paraffin-embedded sections from 73 HCC patients were included in this study. The expression patterns of CAV1 and eNOS determined by immunohistochemistry were correlated with the clinicopathological characteristics and overall survival. Results: Although CAV1 expression did not correlate with any clinicopathological characteristic, increased CAV1 expression was associated with prolonged overall survival (p=0.021), even when using the multivariate Cox's regression model (OR=0.25, 95% CI=0.08-0.72, p=0.011). eNOS expression was correlated with an increased histological grade (p=0.002) and intriguingly, the patients had a decreased overall survival when their lesions presented with high eNOS but low CAV1 expression concomitantly (p=0.003). Meanwhile, the increased CAV1/eNOS merged level determined by immunofluorescence was significantly associated with a decreased histological grade and better overall survival (p=0.023 and 0.001, respectively). Conclusions: Our results suggest CAV1 may play a tumour-suppressive role and can serve as a predictive biomarker in HCC. The impacts of CAV1 on hepatocarcinogenesis may occur partly through its modulation of eNOS.