Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation
BackgroundThe absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic double-stranded DNA(dsDNA) and induces cytokine maturation, release, and pyroptosis. Some studies found that the AIM2 inflammasome was a double-edged sword in many cancers. However...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.998266/full |
| _version_ | 1811206924626034688 |
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| author | Yan Qin Liuxian Pan Tianyu Qin Hanyi Ruan Yujie Zhang Yan Zhang Jianli Li Jianrong Yang Wei Li |
| author_facet | Yan Qin Liuxian Pan Tianyu Qin Hanyi Ruan Yujie Zhang Yan Zhang Jianli Li Jianrong Yang Wei Li |
| author_sort | Yan Qin |
| collection | DOAJ |
| description | BackgroundThe absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic double-stranded DNA(dsDNA) and induces cytokine maturation, release, and pyroptosis. Some studies found that the AIM2 inflammasome was a double-edged sword in many cancers. However, there have been fewer studies on AIM2 inflammasomes in pan-cancer.MethodsGene expression was analyzed using The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database. Immunohistochemistry (IHC) was used to validate the expression of the AIM2. We used the survival curve to explore the prognostic significance of the AIM2 inflammasomes in pan-cancer. Mutations and methylation of AIM2 inflammasome-related genes (AIM2i-RGs) were also comprehensively analyzed. Single sample gene set enrichment analysis was used to calculate the AIM2 inflammasomes score and explore the correlation of the AIM2 inflammasomes score with immune-related genes and immune infiltrations. The function of AIM2 inflammasomes in pan-cancer was analyzed at the single-cell level. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of the AIM2 inflammasomes in the tumor microenvironment.ResultsWe found that AIM2i-RGs were aberrantly expressed in tumors and were strongly associated with prognosis. In pan-cancer, the expression of AIM2i-RGs was positively associated with copy number variation and negatively associated with methylation. In AIM2i-RGs, missense mutations were the predominant type of single nucleotide polymorphism. Moreover, we found that the drugs dimethyloxallyl glycine (DMOG) and Z-LNle-CHO may be sensitive to the AIM2 inflammasomes. The AIM2 inflammasomes score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the AIM2 inflammasomes score was significantly and positively correlated with CD8+ T cell abundance in the tumor microenvironment. Additionally, the AIM2 inflammasomes score was significantly correlated with immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including tumor mutational burden (TMB), microsatellite instability(MSI), and tumor immune dysfunction and exclusion(TIDE). scRNA-seq analysis suggested that AIM2 inflammasomes differ significantly among different cells in the tumor microenvironment. IHC confirmed low expression of AIM2 in colorectal cancer.DiscussionAIM2 inflammasomes may be a new target for future tumor therapy It is likely involved in tumor development, and its high expression may serve as a predictor of tumor immunotherapy efficacy. |
| first_indexed | 2024-04-12T03:55:15Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T03:55:15Z |
| publishDate | 2022-09-01 |
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| spelling | doaj.art-9d02203681c04ab1a3e5ca2871cd4f902022-12-22T03:48:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.998266998266Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validationYan Qin0Liuxian Pan1Tianyu Qin2Hanyi Ruan3Yujie Zhang4Yan Zhang5Jianli Li6Jianrong Yang7Wei Li8Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research center of Health Management, Guangxi Academy of Medical Sciences, Nanning, ChinaDepartment of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research center of Health Management, Guangxi Academy of Medical Sciences, Nanning, ChinaDepartment of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research center of Health Management, Guangxi Academy of Medical Sciences, Nanning, ChinaDepartment of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research center of Health Management, Guangxi Academy of Medical Sciences, Nanning, ChinaDepartment of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research center of Health Management, Guangxi Academy of Medical Sciences, Nanning, ChinaBackgroundThe absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic double-stranded DNA(dsDNA) and induces cytokine maturation, release, and pyroptosis. Some studies found that the AIM2 inflammasome was a double-edged sword in many cancers. However, there have been fewer studies on AIM2 inflammasomes in pan-cancer.MethodsGene expression was analyzed using The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database. Immunohistochemistry (IHC) was used to validate the expression of the AIM2. We used the survival curve to explore the prognostic significance of the AIM2 inflammasomes in pan-cancer. Mutations and methylation of AIM2 inflammasome-related genes (AIM2i-RGs) were also comprehensively analyzed. Single sample gene set enrichment analysis was used to calculate the AIM2 inflammasomes score and explore the correlation of the AIM2 inflammasomes score with immune-related genes and immune infiltrations. The function of AIM2 inflammasomes in pan-cancer was analyzed at the single-cell level. Single-cell transcriptome sequencing (scRNA-seq) data was used to assess the activation state of the AIM2 inflammasomes in the tumor microenvironment.ResultsWe found that AIM2i-RGs were aberrantly expressed in tumors and were strongly associated with prognosis. In pan-cancer, the expression of AIM2i-RGs was positively associated with copy number variation and negatively associated with methylation. In AIM2i-RGs, missense mutations were the predominant type of single nucleotide polymorphism. Moreover, we found that the drugs dimethyloxallyl glycine (DMOG) and Z-LNle-CHO may be sensitive to the AIM2 inflammasomes. The AIM2 inflammasomes score was significantly and positively correlated with the tumor immunity score and the stroma score. In most tumors, the AIM2 inflammasomes score was significantly and positively correlated with CD8+ T cell abundance in the tumor microenvironment. Additionally, the AIM2 inflammasomes score was significantly correlated with immune checkpoint genes in pan-cancer as well as immune checkpoint therapy-related markers including tumor mutational burden (TMB), microsatellite instability(MSI), and tumor immune dysfunction and exclusion(TIDE). scRNA-seq analysis suggested that AIM2 inflammasomes differ significantly among different cells in the tumor microenvironment. IHC confirmed low expression of AIM2 in colorectal cancer.DiscussionAIM2 inflammasomes may be a new target for future tumor therapy It is likely involved in tumor development, and its high expression may serve as a predictor of tumor immunotherapy efficacy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.998266/fullAIM2 inflammasomessingle-cell transcriptome sequencingpan-cancerimmunotherapytumor microenvironment |
| spellingShingle | Yan Qin Liuxian Pan Tianyu Qin Hanyi Ruan Yujie Zhang Yan Zhang Jianli Li Jianrong Yang Wei Li Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation Frontiers in Immunology AIM2 inflammasomes single-cell transcriptome sequencing pan-cancer immunotherapy tumor microenvironment |
| title | Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation |
| title_full | Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation |
| title_fullStr | Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation |
| title_full_unstemmed | Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation |
| title_short | Pan-cancer analysis of AIM2 inflammasomes with potential implications for immunotherapy in human cancer: A bulk omics research and single cell sequencing validation |
| title_sort | pan cancer analysis of aim2 inflammasomes with potential implications for immunotherapy in human cancer a bulk omics research and single cell sequencing validation |
| topic | AIM2 inflammasomes single-cell transcriptome sequencing pan-cancer immunotherapy tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.998266/full |
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