The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses
Abstract Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-03-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-06004-z |
| _version_ | 1797259070271389696 |
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| author | Changfan Qu Hao Cui Song Xiao Longlong Dong Qianyi Lu Lei Zhang Peng Wang Mengyu Xin Hui Zhi Chenyu Liu Shangwei Ning Yue Gao |
| author_facet | Changfan Qu Hao Cui Song Xiao Longlong Dong Qianyi Lu Lei Zhang Peng Wang Mengyu Xin Hui Zhi Chenyu Liu Shangwei Ning Yue Gao |
| author_sort | Changfan Qu |
| collection | DOAJ |
| description | Abstract Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here we present an integrated framework that leverages network-based analyses and Bayesian network inference to identify the regulated relationships including lncRNA, ICP and immunity genes as ICP-related LncRNAs mediated Core Regulatory Circuitry Triplets (ICP-LncCRCTs) that can make robust predictions. Hub ICP-related lncRNAs such as MIR155HG and ADAMTS9-AS2 were highlighted to play central roles in immune regulation. Specific ICP-related lncRNAs could distinguish cancer subtypes. Moreover, the ICP-related lncRNAs are likely to significantly correlated with immune cell infiltration, MHC, CYT. Some ICP-LncCRCTs such as CXCL10-MIR155HG-ICOS could better predict one-, three- and five-year prognosis compared to single molecule in melanoma. We also validated that some ICP-LncCRCTs could effectively predict ICI-response using three kinds of machine learning algorithms follow five independent datasets. Specially, combining ICP-LncCRCTs with the tumor mutation burden (TMB) improves the prediction of ICI-treated melanoma patients. Altogether, this study will improve our grasp of lncRNA functions and accelerating discovery of lncRNA-based biomarkers in ICI treatment. |
| first_indexed | 2024-04-24T23:03:35Z |
| format | Article |
| id | doaj.art-475a8496de7144a0b6c38d3291f85a11 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-24T23:03:35Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-475a8496de7144a0b6c38d3291f85a112024-03-17T12:35:22ZengNature PortfolioCommunications Biology2399-36422024-03-017111410.1038/s42003-024-06004-zThe landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responsesChangfan Qu0Hao Cui1Song Xiao2Longlong Dong3Qianyi Lu4Lei Zhang5Peng Wang6Mengyu Xin7Hui Zhi8Chenyu Liu9Shangwei Ning10Yue Gao11College of Bioinformatics Science and Technology, Harbin Medical UniversityThe Second Affiliated Hospital of Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityThe Second Affiliated Hospital of Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityCollege of Bioinformatics Science and Technology, Harbin Medical UniversityAbstract Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here we present an integrated framework that leverages network-based analyses and Bayesian network inference to identify the regulated relationships including lncRNA, ICP and immunity genes as ICP-related LncRNAs mediated Core Regulatory Circuitry Triplets (ICP-LncCRCTs) that can make robust predictions. Hub ICP-related lncRNAs such as MIR155HG and ADAMTS9-AS2 were highlighted to play central roles in immune regulation. Specific ICP-related lncRNAs could distinguish cancer subtypes. Moreover, the ICP-related lncRNAs are likely to significantly correlated with immune cell infiltration, MHC, CYT. Some ICP-LncCRCTs such as CXCL10-MIR155HG-ICOS could better predict one-, three- and five-year prognosis compared to single molecule in melanoma. We also validated that some ICP-LncCRCTs could effectively predict ICI-response using three kinds of machine learning algorithms follow five independent datasets. Specially, combining ICP-LncCRCTs with the tumor mutation burden (TMB) improves the prediction of ICI-treated melanoma patients. Altogether, this study will improve our grasp of lncRNA functions and accelerating discovery of lncRNA-based biomarkers in ICI treatment.https://doi.org/10.1038/s42003-024-06004-z |
| spellingShingle | Changfan Qu Hao Cui Song Xiao Longlong Dong Qianyi Lu Lei Zhang Peng Wang Mengyu Xin Hui Zhi Chenyu Liu Shangwei Ning Yue Gao The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses Communications Biology |
| title | The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses |
| title_full | The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses |
| title_fullStr | The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses |
| title_full_unstemmed | The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses |
| title_short | The landscape of immune checkpoint-related long non-coding RNAs core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses |
| title_sort | landscape of immune checkpoint related long non coding rnas core regulatory circuitry reveals implications for immunoregulation and immunotherapy responses |
| url | https://doi.org/10.1038/s42003-024-06004-z |
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