To Study Changes in Circulatory Microrna Expression in Hepatocellular Carcinoma Patients Receiving Locoregional Therapy and its Correlation With Therapeutic Response

Abstract

Background and Aim: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Major cause of HCC is underlying Hepatitis B virus (HBV). Due to absence of suitable biomarker; therapeutic response to locoregional therapy is mostly assessed by radiological imaging techniques like DPCT or MRI. There is a need to identify a novel diagnostic and prognostic biomarker for HCC. Circulatory miRNAs are considered as potential biomarker due to their ease in detection and high stability in circulation. The study was done to evaluate the level of miR-21, -221 and -16 in HCC patients before and after locoregional therapy. Methods: Circulatory miRNA profiling of 84 miRNAs that are differentially expressed in serum was carried out using miRNA PCR Array in healthy and HBV infected treatment naïve, cirrhotic and HCC patients (n = 32). These miRNAs expression was normalized using both endogenous and exogenous miRNAs expression and differential miRNA array data was analyzed by comparative Ct method for fold changes. The HCC patients were staged and treated as per BCLC criteria and therapeutic response was assessed by mRECIST criteria. The correlations of selected miRNA (-21, -221 and -16) expressions in pre and post locoregional therapy were assed for therapeutic response. Results: Differential expression profiling of 84 miRNAs in serum of healthy vs CHB, cirrhotic and HCC patient have shown significant up-regulation for 2 (1.4–6.46 fold), 9 (1.02–14.28 fold) and 5 (1.40–74.54) miRNA after normalization with exogenous Cel miR39 and endogenous SNORD95. The miRNAs (miR-16, -21 and -221) upregulated in HCC were further evaluated for changes in expression during locoregional therapy at baseline and one month post-therapy (n = 30). The significant down regulation of these miRNAs were associated with complete response to locoregional therapy. Conclusion: These miRNA may act as prognostic and therapeutic marker in HCC patients receiving locoregional therapy.