Molecular profiling of tissue and circulating cancer-related ncRNA in hepatocellular carcinoma

Human hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer-related death. Non-coding RNAs (ncRNAs), including miRNAs and long ncRNAs (lncRNAs), play a role in almost all aspects of cancer biology and have emerged as novel therapeutic targets and valuable candidates with clinical translational potential in cancer management. In HCC, we have described the tumor suppressor roles of miR-193a-3p and miR-23b-3p, and we have identified the dysregulation of lncRNA GAS5 and miR-126-3p in HCC cells treated with sorafenib, a multikinase inhibitor used for the treatment of advanced HCC. Here, to further elucidate the function of these ncRNAs in HCC and assess their potential as molecular indicators, we evaluated the levels of the selected ncRNAs in tissue and liquid biopsies of HCC patients. The expression of miR-193a-3p, miR-23b-3p, and miR-126-3p was significantly reduced in HCCs compared to peritumoral tissues. Interestingly, high miR-193a-3p levels in HCCs were associated with prolonged OS and DFS of patients. Regarding the circulating levels of the selected ncRNAs, miR-193a-3p resulted undetectable, whereas miR-23b-3p and GAS5 were lower and miR-126-3p was higher in plasma of HCC patients versus healthy individuals. The ROC curve analysis underlined the diagnostic relevance of all the aforementioned ncRNAs. Finally, miR-23b-3p, miR-126-3p and GAS5 were preliminarily evaluated in longitudinally collected plasma from a small group of HCC patients treated with sorafenib (n=7). The results showed variations in the levels of these ncRNAs during the follow-up, and interestingly miR-23b-3p significantly increased one month after sorafenib treatment. Overall, these data highlight the promising translational relevance of the selected ncRNAs in HCC and their potential involvement in the response to sorafenib treatment