Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy
PurposeTo construct an immune-related gene prognostic index (IRGPI) for colon cancer and elucidate the molecular and immune characteristics as well as the benefit of immune checkpoint inhibitor (ICI) therapy in IRGPI-defined groups of colon cancer.Experimental DesignTranscriptional and clinical data...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.802665/full |
| _version_ | 1818476583111884800 |
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| author | Zheng Wang Jingru Song Jingru Song Nisma Lena Bahaji Azami Nisma Lena Bahaji Azami Mingyu Sun Mingyu Sun |
| author_facet | Zheng Wang Jingru Song Jingru Song Nisma Lena Bahaji Azami Nisma Lena Bahaji Azami Mingyu Sun Mingyu Sun |
| author_sort | Zheng Wang |
| collection | DOAJ |
| description | PurposeTo construct an immune-related gene prognostic index (IRGPI) for colon cancer and elucidate the molecular and immune characteristics as well as the benefit of immune checkpoint inhibitor (ICI) therapy in IRGPI-defined groups of colon cancer.Experimental DesignTranscriptional and clinical data of colon cancer samples were obtained from The Cancer Genome Atlas (TCGA) (n = 521). Immune-related genes were obtained from ImmPort and InnateDB databases. 21 immune-related hub genes were identified byweighted gene co-expression network analysis (WGCNA). the Cox regression method was used to construct IRGPI and validated with Gene Expression Omnibus (GEO) dataset (n = 584). Finally, the molecular and immune profiles in the groups defined by IRGPI and the benefit of ICI treatment were analyzed.Results8 genes were identified to construct IRGPI. IRGPI-low group had a better overall survival (OS) than IRGPI-high group. And this was well validated in the GEO cohort. Overall results showed that those with low IRGPI scores were enriched in antitumor metabolism, and collated with high infiltration of resting memory CD4 T cells and less aggressive phenotypes, benefiting more from ICI treatment. Conversely, high IRGPI scores were associated with cell adhesion molecules (CAMs) and chemokine signaling pathways, high infiltration of macrophage M1, suppressed immunity, more aggressive colon cancer phenotypes, as well as reduced therapeutic benefit from ICI treatment.ConclusionsIRGPI is a promising biomarker to differentiate the prognostic and molecular profile of colon cancer, as well as the therapeutic benefits of ICI treatment. |
| first_indexed | 2024-12-10T09:27:39Z |
| format | Article |
| id | doaj.art-1125bf25d56b42afa8e94921692ffd6a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T09:27:39Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1125bf25d56b42afa8e94921692ffd6a2022-12-22T01:54:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.802665802665Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to ImmunotherapyZheng Wang0Jingru Song1Jingru Song2Nisma Lena Bahaji Azami3Nisma Lena Bahaji Azami4Mingyu Sun5Mingyu Sun6Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaShanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Liver and Kidney Diseases, Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaPurposeTo construct an immune-related gene prognostic index (IRGPI) for colon cancer and elucidate the molecular and immune characteristics as well as the benefit of immune checkpoint inhibitor (ICI) therapy in IRGPI-defined groups of colon cancer.Experimental DesignTranscriptional and clinical data of colon cancer samples were obtained from The Cancer Genome Atlas (TCGA) (n = 521). Immune-related genes were obtained from ImmPort and InnateDB databases. 21 immune-related hub genes were identified byweighted gene co-expression network analysis (WGCNA). the Cox regression method was used to construct IRGPI and validated with Gene Expression Omnibus (GEO) dataset (n = 584). Finally, the molecular and immune profiles in the groups defined by IRGPI and the benefit of ICI treatment were analyzed.Results8 genes were identified to construct IRGPI. IRGPI-low group had a better overall survival (OS) than IRGPI-high group. And this was well validated in the GEO cohort. Overall results showed that those with low IRGPI scores were enriched in antitumor metabolism, and collated with high infiltration of resting memory CD4 T cells and less aggressive phenotypes, benefiting more from ICI treatment. Conversely, high IRGPI scores were associated with cell adhesion molecules (CAMs) and chemokine signaling pathways, high infiltration of macrophage M1, suppressed immunity, more aggressive colon cancer phenotypes, as well as reduced therapeutic benefit from ICI treatment.ConclusionsIRGPI is a promising biomarker to differentiate the prognostic and molecular profile of colon cancer, as well as the therapeutic benefits of ICI treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2022.802665/fullcolon cancerimmune-related gene prognostic indexweighted gene co-expression network analysis (WGCNA)prognosissignature |
| spellingShingle | Zheng Wang Jingru Song Jingru Song Nisma Lena Bahaji Azami Nisma Lena Bahaji Azami Mingyu Sun Mingyu Sun Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy Frontiers in Immunology colon cancer immune-related gene prognostic index weighted gene co-expression network analysis (WGCNA) prognosis signature |
| title | Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy |
| title_full | Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy |
| title_fullStr | Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy |
| title_full_unstemmed | Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy |
| title_short | Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy |
| title_sort | identification of a novel immune landscape signature for predicting prognosis and response of colon cancer to immunotherapy |
| topic | colon cancer immune-related gene prognostic index weighted gene co-expression network analysis (WGCNA) prognosis signature |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.802665/full |
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