Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas
Abstract Background Small peptides encoded by long non-coding RNAs (lncRNAs) have attracted attention for their various functions. Recent studies indicate that these small peptides participate in immune responses and antigen presentation. However, the significance of RNA modifications remains unclea...
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BMC
2022-10-01
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Series: | Journal of Translational Medicine |
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Online Access: | https://doi.org/10.1186/s12967-022-03713-z |
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author | Wenbo Zhao Yibo Wu Feihu Zhao Zhiyi Xue Wenyu Liu Zenxin Cao Zhimin Zhao Bin Huang Mingzhi Han Xingang Li |
author_facet | Wenbo Zhao Yibo Wu Feihu Zhao Zhiyi Xue Wenyu Liu Zenxin Cao Zhimin Zhao Bin Huang Mingzhi Han Xingang Li |
author_sort | Wenbo Zhao |
collection | DOAJ |
description | Abstract Background Small peptides encoded by long non-coding RNAs (lncRNAs) have attracted attention for their various functions. Recent studies indicate that these small peptides participate in immune responses and antigen presentation. However, the significance of RNA modifications remains unclear. Methods Thirteen non-m6A-related neoantigen-coding lncRNAs were selected for analysis from the TransLnc database. Next, a neoantigen activation score (NAS) model was established based on the characteristics of the lncRNAs. Machine learning was employed to expand the model to two additional RNA-seq and two single-cell sequencing datasets for further validation. The DLpTCR algorithm was used to predict T cell receptor (TCR)-peptide binding probability. Results The non-m6A-related NAS model predicted patients’ overall survival outcomes more precisely than the m6A-related NAS model. Furthermore, the non-m6A-related NAS was positively correlated with tumor cells’ evolutionary level, immune infiltration, and antigen presentation. However, high NAS gliomas also showed more PD-L1 expression and high mutation frequencies of T-cell positive regulators. Interestingly, results of intercellular communication analysis suggest that T cell-high neoplastic cell interaction is weaker in both of the NAS groups which might arise from decreased IFNGR1 expression. Moreover, we identified unique TCR-peptide pairs present in all glioma samples based on peptides encoded by the 13 selected lncRNAs. And increased levels of neoantigen-active TCR patterns were found in high NAS gliomas. Conclusions Our work suggests that non-m6A-related neoantigen-coding lncRNAs play an essential role in glioma progression and that screened TCR clonotypes might provide potential avenues for chimeric antigen receptor T cell (CAR-T) therapy for gliomas. |
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last_indexed | 2024-04-12T17:51:50Z |
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spelling | doaj.art-75e744987c1e4d918ca3e252a6c3e8a52022-12-22T03:22:29ZengBMCJournal of Translational Medicine1479-58762022-10-0120112310.1186/s12967-022-03713-zScoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomasWenbo Zhao0Yibo Wu1Feihu Zhao2Zhiyi Xue3Wenyu Liu4Zenxin Cao5Zhimin Zhao6Bin Huang7Mingzhi Han8Xingang Li9Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong UniversityAbstract Background Small peptides encoded by long non-coding RNAs (lncRNAs) have attracted attention for their various functions. Recent studies indicate that these small peptides participate in immune responses and antigen presentation. However, the significance of RNA modifications remains unclear. Methods Thirteen non-m6A-related neoantigen-coding lncRNAs were selected for analysis from the TransLnc database. Next, a neoantigen activation score (NAS) model was established based on the characteristics of the lncRNAs. Machine learning was employed to expand the model to two additional RNA-seq and two single-cell sequencing datasets for further validation. The DLpTCR algorithm was used to predict T cell receptor (TCR)-peptide binding probability. Results The non-m6A-related NAS model predicted patients’ overall survival outcomes more precisely than the m6A-related NAS model. Furthermore, the non-m6A-related NAS was positively correlated with tumor cells’ evolutionary level, immune infiltration, and antigen presentation. However, high NAS gliomas also showed more PD-L1 expression and high mutation frequencies of T-cell positive regulators. Interestingly, results of intercellular communication analysis suggest that T cell-high neoplastic cell interaction is weaker in both of the NAS groups which might arise from decreased IFNGR1 expression. Moreover, we identified unique TCR-peptide pairs present in all glioma samples based on peptides encoded by the 13 selected lncRNAs. And increased levels of neoantigen-active TCR patterns were found in high NAS gliomas. Conclusions Our work suggests that non-m6A-related neoantigen-coding lncRNAs play an essential role in glioma progression and that screened TCR clonotypes might provide potential avenues for chimeric antigen receptor T cell (CAR-T) therapy for gliomas.https://doi.org/10.1186/s12967-022-03713-zGliomaLncRNANon-m6A modificationMachine learningNeoantigenImmunotherapy |
spellingShingle | Wenbo Zhao Yibo Wu Feihu Zhao Zhiyi Xue Wenyu Liu Zenxin Cao Zhimin Zhao Bin Huang Mingzhi Han Xingang Li Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas Journal of Translational Medicine Glioma LncRNA Non-m6A modification Machine learning Neoantigen Immunotherapy |
title | Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas |
title_full | Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas |
title_fullStr | Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas |
title_full_unstemmed | Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas |
title_short | Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas |
title_sort | scoring model based on the signature of non m6a related neoantigen coding lncrnas assists in immune microenvironment analysis and tcr neoantigen pair selection in gliomas |
topic | Glioma LncRNA Non-m6A modification Machine learning Neoantigen Immunotherapy |
url | https://doi.org/10.1186/s12967-022-03713-z |
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