Differential Expression of MicroRNA in Non-tumoral Liver Tissue of Patients With Non-alcoholic Steatohepatitis Cirrhosis and Hepatocellular Cancer

Abstract

Introduction: Patients with NASH cirrhosis are at risk for developing hepatocellular cancer (HCC). Due to unpredictable risk of progression, all cirrhosis patients are recommended to undergo surveillance. MicroRNAs (miRNAs) play important roles in the development and progression of HCC, and it is quite possible that certain miRNAs in the non-tumor cirrhotic tissue may serve as a biomarker for subsequent development of HCC. The aim of the current study is to identify differentially expressed miRNAs in nontumor cirrhotic tissue of patients with NASH cirrhosis with and without HCC. Methods: miRNA expression profile using the Thermo Scientific Dharmacon RNAi Discovery platform was obtained from non-tumoral liver explant tissue of NASH cirrhosis with HCC (n=5), without HCC (n=12), and control (n=24; 12 tumor adjacent normal tissue with no chronic liver disease +12 normal liver biopsies of patients suspected with NAFLD). Differentially expressed miRNAs between 2 set of conditions (ex: HCC vs. NASH cirrhosis) were determined by performing student t-test and filtered at a p<0.01. Real-time PCR was performed to confirm the differentially expressed miRNAs microarray data. Results: NASH cirrhosis patients with and without HCC were similar in age, gender, race, BMI (36±2 vs. 30±7 kg/m2), and MELD score (13±5 vs. 13±6). Several miRNAs were statistically differentially expressed in HCC when compared to cirrhosis (miRNAs=8) and controls (miRNA =144). The 8 miRNAs that were significantly different between HCC and NASH cirrhosis with fold change are shown Table 1. A decrease in expression was seen with HCC compared to NASH cirrhosis or normal liver. Gene prediction analysis identified several genes controlled by these differentially expressed miRNA. Notable among these genes was kinase suppressor of RAS 2 (KSR2) gene, known to be associated with hepatocellular cancer.Table 1Conclusion: Eight miRNAs are differentially expressed in non-tumoral cirrhotic tissue in patients with HCC. Recognition of these hepatic miRNAs in patients with NASH cirrhosis may help identify the risk of subsequent HCC development.