Decreased Expression Of Iron Regulatory Protein-1 In Hepatocellular Carcinoma Associates With Poor Prognosis

Background: Iron regulatory protein-1 (IRP1) plays a critical role in cellular iron homeostasis and in the TCA cycle, which are closely associated with cancer development. However, the diagnostic and prognostic value of IRP1 in hepatocellular carcinoma (HCC) was not still estimated. Therefore, it was necessary to verify its expression and significance in patients with HCC in this study. Methods: The expression of IRP1 was analyzed in 42 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues) and 191 paraffin-embedded HCC sections using immunohistochemistry (IHC). Then, receivers operating characteristic curve (ROC), Kaplan-Meier and Cox regression analysis were applied to evaluate the potential diagnostic and prognostic value of IRP1, respectively. Results: IRP1 expression level was significantly decreased in HCC tissues compared to the corresponding adjacent nontumorous liver tissues (P = 0.0003). Further correlation analyses indicated that the expression of IRP1 was significantly associated with TNM stage (P = 0.008) and vascular invasion (P = 0.008). ROC analysis showed the AUC was 0.765, and the optimal cutoff value of integrated optical density was 40860000, providing a sensitivity of 64.29% and a specificity of 76.19%. Moreover, overall survival (OS) and time to recurrence (TTR) analyses showed HCC patients with low IRP1 expression had lower survival rate (P = 0.007) and higher recurrence rate (P = 0.033). Furthermore, multivariate analysis showed that IRP1 was an independent prognostic factor for TTR (HR = 0.616, 95% CI = 0.398-0.952, P = 0.029). Conclusion: Collectively, our study demonstrated that IRP1 could be served as a potential diagnostic and prognostic marker for HCC patients.