Discovery of High-Expressing lncRNA-Derived sORFs as Potential Tumor-associated Antigens in Hepatocellular Carcinoma

Abstract Background This study focuses on a comprehensive analysis of ribosome profiling (Ribo-seq) data to identify long non-coding RNAs (lncRNAs) with elevated expression of small open reading frames (sORFs) in Hepatocellular Carcinoma (HCC). The investigation explores the emerging role of sORFs as potential tumor-specific epitopes, contributing insights to tumor immunotherapy. Methods The identification of sORFs was facilitated using the MetamORF database, employing a meticulous analysis of ribosome profiling data within HCC-associated lncRNAs. Translation efficiency was assessed, and epitope prediction was performed using the pVACbind tool. To determine the existence of micropeptides originating from sORFs, a peptide search was conducted. validated translational activity and identified potential epitopes. Results Our findings reveal increased translation efficiency in HCC-associated lncRNAs compared to normal tissues. Notably, ORF3418981 demonstrates the highest expression, supported by experimental evidence at the protein level. Epitope prediction identifies a putative epitope at ORF3418981's C-terminus. Conclusion The importance of lncRNA-derived sORFs in HCC is highlighted by this work, which connects the fields of tumor immunotherapy and non-coding RNA biology. Finding particular lncRNAs that have increased translation, like ORF3418981, points to possible therapeutic targets for the treatment of HCC. These revelations offer a basis for comprehending lncRNA-derived sORFs' translational and protein-coding abilities in relation to HCC.