Abstract：
BACKGROUND: This study is based on deep mining of Ribo-seq data for the identification of lncRNAs that have highly expressed sORFs in HCC. In this paper, dynamic prospects associated with sORFs acting as newly defined tumor-specific epitopes are discussed with possible improvement in strategies for tumor immunotherapy.
OBJECTIVE: Using ribosome profiling to identify and characterize sORFs within lncRNAs in HCC, identify potential therapeutic targets and tumor-specific epitopes applicable for immunotherapy.
METHODS: MetamORF performed the identification of sORFs with deep analysis of the data of ribosome profiling in lncRNAs associated with HCC. The translation efficiency in these molecules was estimated, and epitope prediction was done by pVACbind. Peptide search was done to check the presence of micropeptides translated from these identified sORFs. validated translational activity and identified potential epitopes.
RESULTS: Higher translation efficiency was noted in the case of lncRNAs associated with HCC compared to normal tissues. Of particular note is ORF3418981, which results in the highest expression and has supporting experimental evidence at the protein level. Epitope prediction identified a putative epitope at the C-terminus of ORF3418981.
CONCLUSIONS: This study uncovers the as-yet-unknown potential of lncRNA-derived sORFs as sources of tumor antigens, shifting the research focus from protein-coding genes to non-coding RNAs also in the HCC context. Moreover, this study highlights the contribution of a subset of lncRNAs, especially LINC00152, to the development of tumors and modulation of the immune response by its sORFs.
OBJECTIVE: Using ribosome profiling to identify and characterize sORFs within lncRNAs in HCC, identify potential therapeutic targets and tumor-specific epitopes applicable for immunotherapy.
METHODS: MetamORF performed the identification of sORFs with deep analysis of the data of ribosome profiling in lncRNAs associated with HCC. The translation efficiency in these molecules was estimated, and epitope prediction was done by pVACbind. Peptide search was done to check the presence of micropeptides translated from these identified sORFs. validated translational activity and identified potential epitopes.
RESULTS: Higher translation efficiency was noted in the case of lncRNAs associated with HCC compared to normal tissues. Of particular note is ORF3418981, which results in the highest expression and has supporting experimental evidence at the protein level. Epitope prediction identified a putative epitope at the C-terminus of ORF3418981.
CONCLUSIONS: This study uncovers the as-yet-unknown potential of lncRNA-derived sORFs as sources of tumor antigens, shifting the research focus from protein-coding genes to non-coding RNAs also in the HCC context. Moreover, this study highlights the contribution of a subset of lncRNAs, especially LINC00152, to the development of tumors and modulation of the immune response by its sORFs.
摘要：
背景：这项研究基于Ribo-seq数据的深度挖掘，用于鉴定在HCC中高度表达sORF的lncRNAs。在本文中,讨论了与作为新定义的肿瘤特异性表位的sORF相关的动态前景,并讨论了肿瘤免疫治疗策略的可能改进.
目的：使用核糖体谱分析来鉴定和表征HCC中lncRNAs内的sORFs，确定适用于免疫治疗的潜在治疗靶点和肿瘤特异性表位。
方法：MetamORF通过深入分析与HCC相关的lncRNAs的核糖体谱分析数据来鉴定sORFs。估计了这些分子的翻译效率，通过pVAC结合进行表位预测。进行肽搜索以检查从这些鉴定的sORF翻译的微肽的存在。验证翻译活性并鉴定潜在表位。
结果：与正常组织相比，与HCC相关的lncRNAs的翻译效率更高。特别值得注意的是ORF3418981,其导致最高表达并且在蛋白质水平上具有支持的实验证据。表位预测鉴定了ORF3418981的C末端的推定表位。
结论：本研究揭示了lncRNA来源的sORF作为肿瘤抗原来源的未知潜力，在HCC的背景下，研究重点也从蛋白质编码基因转移到非编码RNA。此外，这项研究强调了lncRNAs子集的贡献，特别是LINC00152，用于肿瘤的发展和其sORF对免疫反应的调节。
目的：使用核糖体谱分析来鉴定和表征HCC中lncRNAs内的sORFs，确定适用于免疫治疗的潜在治疗靶点和肿瘤特异性表位。
方法：MetamORF通过深入分析与HCC相关的lncRNAs的核糖体谱分析数据来鉴定sORFs。估计了这些分子的翻译效率，通过pVAC结合进行表位预测。进行肽搜索以检查从这些鉴定的sORF翻译的微肽的存在。验证翻译活性并鉴定潜在表位。
结果：与正常组织相比，与HCC相关的lncRNAs的翻译效率更高。特别值得注意的是ORF3418981,其导致最高表达并且在蛋白质水平上具有支持的实验证据。表位预测鉴定了ORF3418981的C末端的推定表位。
结论：本研究揭示了lncRNA来源的sORF作为肿瘤抗原来源的未知潜力，在HCC的背景下，研究重点也从蛋白质编码基因转移到非编码RNA。此外，这项研究强调了lncRNAs子集的贡献，特别是LINC00152，用于肿瘤的发展和其sORF对免疫反应的调节。
