Comprehensive analysis of a ceRNA network associated with TP53 mutations in liver hepatocellular carcinoma

Abstract Liver cancer is one of the most common causes of cancer-related death and is quantitatively dominated by the liver hepatocellular carcinoma (HCC) subtype. Although advances have been made in recent years, further exploration on new HCC carcinogenic mechanisms as well as diagnostic and therapeutic methods in the context of detrimental TP53 abnormalities is indispensable on the way to conquer HCC. In this study, competing endogenous RNA (ceRNA) network was constructed on tumor samples stratified by the TP53 mutational status. With demonstrated TP53 mutant-specificity, the network nodes including AC017104.6, RP5-1092A11.5, RP11-365O16.6 and PTBP1 were all prognosis-related. Further therapeutic correlation analysis unveiled the connection between their expressions and tumor microenvironment fluctuation as well as possible chemotherapy resistance. Additionally, we explored the drug sensitivity difference between TP53 wild type and mutant samples, complementing the therapeutic arsenal of HCC. The universality of the key node PTBP1 was verified by multi-source transcriptional and protein level expressions. Taken together, this is the first study focusing on the ceRNA network mediated by TP53 mutations and its provoked therapeutic associations in HCC. Our results deepened the understanding of the concomitant alternations brought by TP53 mutations and could benefit future therapeutic development in HCC.