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A Study of MicroRNA-24 Expression in Aflatoxin B1 Exposed Patients with Hepatocellular Carcinoma and Cirrhosis

Afaf M Attia, Dina Elhammady, Maha R Habeeb, Neven F Abbas and Maysaa El Sayed Zaki

Introduction: Over 80% of hepatocellular carcinoma (HCC) sufferers occur in developing countries as a result of exposure to hepatitis B or C viruses, through formation of cirrhosis or viral integration into host DNA on the part of HBV, or due to ingestion of aflatoxin B1 (AFB1) causing DNA damage in hepatic tissue with generation of mutations, particularly in p53 tumor suppressor gene. MicroRNAs are noncoding RNAs that have an effect on oncogene and tumor suppressor gene expression, hence partaking in carcinogenesis. A connection between HCC and dysregulated expression of microRNAs has been repeatedly demonstrated, suggesting that circulating microRNAs might potentially be used as biomarkers for pre-clinical HCC detection. We aimed in this study to assess the role of micro-ribonucleic acid-24 (microRNA-24) expression in patients with cirrhosis and HCC who have experienced high levels of AFB1 exposure.
Materials and Methods: Fifty HCC and 24 hepatic cirrhosis patients, in addition to 20 healthy control subjects were included in this study. Aflatoxin B1 was measured by enzyme-linked immunosorbent assay (ELISA) and microRNA-24 was detected using real-time polymerase chain reaction (real-time PCR).
Results: Both aflatoxin B1 levels and microRNA-24 expression were found to be significantly increased in all patient groups in comparison to controls, more so in the HCC than cirrhotic group (p˂0.0001). A highly significant correlation was detected between levels of AFB1 and amount of microRNA-24 expressed in both patient groups relative to their control counterparts (p˂0.0001). Receiver Operating Characteristic (ROC) curve performed to evaluate the ability of microRNA-24 to differentiate between HCC and cirrhosis showed that it had sensitivity of 80% and specificity of 63% at cutoff 1.3, which was highly significant (p˂0.0001).
Conclusion: Increased aflatoxin B1 levels detected in patients with cirrhosis and HCC further support previous studies evaluating the level of exposure of the Egyptian population to this carcinogen and support the critical role of aflatoxin B1 in the appearance of HCC. In addition, microRNA-24 expression levels demonstrated in both cirrhosis and HCC might be valuable for use as a noninvasive diagnostic tool for diagnosis of HCC.