Analysis of HERV signature and their contributions in hepatitis B and C virus-associated hepatocellular carcinoma

Human endogenous retroviruses (HERVs) constitute about one-tenth of the human genome as DNA remnants of ancient retroviral infections inherited by vertical transmission in the germ line. HERVs stay in the middle between being self-molecules and microbial antigens as the human immune defences can tolerate them, but they have also been associated with the occurrence of neurological disorders, autoimmune diseases and cancer. Moreover, considering the hypothesis of HERVs’ transactivation due to viral infections, HERVs might have an important role in viral infection-induced tumours, such as Hepatocellular Carcinoma (HCC). HCC is one of the most diffuse and deadly cancer diseases worldwide and has HCV and HBV infections as the most relevant etiologic factors. The mechanisms of HERVs’ involvement in HCC have been partially explored, but still remain largely unclear. Moreover, the interplay between HERVs and HCV/HBV infections in viral-induced HCC has been poorly investigated. Thus, this study aimed to analyse HERVs’ modulation in viral-induced HCC in three different transcriptomic datasets through the combination of bioinformatic analyses and wet lab procedures. In all these datasets, the obtained findings highlighted the impact of HCC condition on HERV expression, according to the overall clustering of the samples and the identification of several differentially expressed HERVs. Thus, the present thesis provides a comprehensive knowledge of HERV transcriptome in HCC, laying the bases for the characterization of HERVs’ involvement in this tumour in association with HCV and HBV and their synergy in viral-induced HCC. In addition, the obtained findings have the potential to improve the disease understanding and open to new treatments and diagnostic options, including HERVs’ exploitation as biomarkers or innovative drug targets for HCC.