We speculate that IR overexpression in HCC might be caused by hypoxia, which is known to promote HCC progression: Roudnicky et al. demonstrated in bladder cancer that hypoxia upregulated IR expression in vitro.17 IR upregulation was mediated by the hypoxia-inducible factor-1α (HIF-1α). This evidence concerns the gene HIF1A and urinary bladder carcinoma.