PMID- 33363023 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201229 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 10 DP - 2020 TI - Systematically Characterizing A-to-I RNA Editing Neoantigens in Cancer. PG - 593989 LID - 10.3389/fonc.2020.593989 [doi] LID - 593989 AB - A-to-I RNA editing can contribute to the transcriptomic and proteomic diversity of many diseases including cancer. It has been reported that peptides generated from RNA editing could be naturally presented by human leukocyte antigen (HLA) molecules and elicit CD8+ T cell activation. However, a systematical characterization of A-to-I RNA editing neoantigens in cancer is still lacking. Here, an integrated RNA-editing based neoantigen identification pipeline PREP (Prioritizing of RNA Editing-based Peptides) was presented. A comprehensive RNA editing neoantigen profile analysis on 12 cancer types from The Cancer Genome Atlas (TCGA) cohorts was performed. PREP was also applied to 14 ovarian tumor samples and two clinical melanoma cohorts treated with immunotherapy. We finally proposed an RNA editing neoantigen immunogenicity score scheme, i.e. REscore, which takes RNA editing level and infiltrating immune cell population into consideration. We reported variant peptide from protein IFI30 in breast cancer which was confirmed expressed and presented in two samples with mass spectrometry data support. We showed that RNA editing neoantigen could be identified from RNA-seq data and could be validated with mass spectrometry data in ovarian tumor samples. Furthermore, we characterized the RNA editing neoantigen profile of clinical melanoma cohorts treated with immunotherapy. Finally, REscore showed significant associations with improved overall survival in melanoma cohorts treated with immunotherapy. These findings provided novel insights of cancer biomarker and enhance our understanding of neoantigen derived from A-to-I RNA editing as well as more types of candidates for personalized cancer vaccines design in the context of cancer immunotherapy. CI - Copyright (c) 2020 Zhou, Wei, Zhang, Yang and Liu. FAU - Zhou, Chi AU - Zhou C AD - Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Bioinformatics Department, School of Life Sciences and Technology, Tongji University, Shanghai, China. FAU - Wei, Zhiting AU - Wei Z AD - Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Bioinformatics Department, School of Life Sciences and Technology, Tongji University, Shanghai, China. FAU - Zhang, Liye AU - Zhang L AD - School of Life Science and Technology, ShanghaiTech University, Shanghai, China. FAU - Yang, Zhaoyi AU - Yang Z AD - Department of Pharmacy, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China. FAU - Liu, Qi AU - Liu Q AD - Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Bioinformatics Department, School of Life Sciences and Technology, Tongji University, Shanghai, China. LA - eng PT - Journal Article DEP - 20201210 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC7758481 OTO - NOTNLM OT - RNA editing OT - cancer immunotherapy OT - melanoma OT - neoantigen identification OT - predictive biomarker COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2020/12/29 06:00 MHDA- 2020/12/29 06:01 PMCR- 2020/01/01 CRDT- 2020/12/28 11:57 PHST- 2020/08/12 00:00 [received] PHST- 2020/11/09 00:00 [accepted] PHST- 2020/12/28 11:57 [entrez] PHST- 2020/12/29 06:00 [pubmed] PHST- 2020/12/29 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2020.593989 [doi] PST - epublish SO - Front Oncol. 2020 Dec 10;10:593989. doi: 10.3389/fonc.2020.593989. eCollection 2020.