Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma
IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibito...
Ausführliche Beschreibung
Autor*in: |
Zhongqing Liang [verfasserIn] Ruolan Sun [verfasserIn] Pengcheng Tu [verfasserIn] Yan Liang [verfasserIn] Li Liang [verfasserIn] Fuyan Liu [verfasserIn] Yong Bian [verfasserIn] Gang Yin [verfasserIn] Fan Zhao [verfasserIn] Mingchen Jiang [verfasserIn] Junfei Gu [verfasserIn] Decai Tang [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Schlagwörter: |
immune-related gene prognostic index (IRGPI) |
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Übergeordnetes Werk: |
In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022) |
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Übergeordnetes Werk: |
volume:13 ; year:2022 |
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DOI / URN: |
10.3389/fimmu.2022.944286 |
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Katalog-ID: |
DOAJ085249610 |
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520 | |a IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. | ||
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650 | 4 | |a immune-related gene prognostic index (IRGPI) | |
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653 | 0 | |a Immunologic diseases. Allergy | |
700 | 0 | |a Ruolan Sun |e verfasserin |4 aut | |
700 | 0 | |a Pengcheng Tu |e verfasserin |4 aut | |
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700 | 0 | |a Yan Liang |e verfasserin |4 aut | |
700 | 0 | |a Li Liang |e verfasserin |4 aut | |
700 | 0 | |a Fuyan Liu |e verfasserin |4 aut | |
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700 | 0 | |a Junfei Gu |e verfasserin |4 aut | |
700 | 0 | |a Decai Tang |e verfasserin |4 aut | |
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10.3389/fimmu.2022.944286 doi (DE-627)DOAJ085249610 (DE-599)DOAJ3ff9ed819dce4b81bf79b5a661d1059a DE-627 ger DE-627 rakwb eng RC581-607 Zhongqing Liang verfasserin aut Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. colorectal carcinoma immune-related gene prognostic index (IRGPI) tumor immune microenvironment (TIM) immune-related gene (IRG) immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy Ruolan Sun verfasserin aut Pengcheng Tu verfasserin aut Pengcheng Tu verfasserin aut Yan Liang verfasserin aut Li Liang verfasserin aut Fuyan Liu verfasserin aut Yong Bian verfasserin aut Yong Bian verfasserin aut Gang Yin verfasserin aut Fan Zhao verfasserin aut Mingchen Jiang verfasserin aut Junfei Gu verfasserin aut Decai Tang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.944286 kostenfrei https://doaj.org/article/3ff9ed819dce4b81bf79b5a661d1059a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.944286/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
spelling |
10.3389/fimmu.2022.944286 doi (DE-627)DOAJ085249610 (DE-599)DOAJ3ff9ed819dce4b81bf79b5a661d1059a DE-627 ger DE-627 rakwb eng RC581-607 Zhongqing Liang verfasserin aut Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. colorectal carcinoma immune-related gene prognostic index (IRGPI) tumor immune microenvironment (TIM) immune-related gene (IRG) immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy Ruolan Sun verfasserin aut Pengcheng Tu verfasserin aut Pengcheng Tu verfasserin aut Yan Liang verfasserin aut Li Liang verfasserin aut Fuyan Liu verfasserin aut Yong Bian verfasserin aut Yong Bian verfasserin aut Gang Yin verfasserin aut Fan Zhao verfasserin aut Mingchen Jiang verfasserin aut Junfei Gu verfasserin aut Decai Tang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.944286 kostenfrei https://doaj.org/article/3ff9ed819dce4b81bf79b5a661d1059a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.944286/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
allfields_unstemmed |
10.3389/fimmu.2022.944286 doi (DE-627)DOAJ085249610 (DE-599)DOAJ3ff9ed819dce4b81bf79b5a661d1059a DE-627 ger DE-627 rakwb eng RC581-607 Zhongqing Liang verfasserin aut Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. colorectal carcinoma immune-related gene prognostic index (IRGPI) tumor immune microenvironment (TIM) immune-related gene (IRG) immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy Ruolan Sun verfasserin aut Pengcheng Tu verfasserin aut Pengcheng Tu verfasserin aut Yan Liang verfasserin aut Li Liang verfasserin aut Fuyan Liu verfasserin aut Yong Bian verfasserin aut Yong Bian verfasserin aut Gang Yin verfasserin aut Fan Zhao verfasserin aut Mingchen Jiang verfasserin aut Junfei Gu verfasserin aut Decai Tang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.944286 kostenfrei https://doaj.org/article/3ff9ed819dce4b81bf79b5a661d1059a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.944286/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
allfieldsGer |
10.3389/fimmu.2022.944286 doi (DE-627)DOAJ085249610 (DE-599)DOAJ3ff9ed819dce4b81bf79b5a661d1059a DE-627 ger DE-627 rakwb eng RC581-607 Zhongqing Liang verfasserin aut Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. colorectal carcinoma immune-related gene prognostic index (IRGPI) tumor immune microenvironment (TIM) immune-related gene (IRG) immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy Ruolan Sun verfasserin aut Pengcheng Tu verfasserin aut Pengcheng Tu verfasserin aut Yan Liang verfasserin aut Li Liang verfasserin aut Fuyan Liu verfasserin aut Yong Bian verfasserin aut Yong Bian verfasserin aut Gang Yin verfasserin aut Fan Zhao verfasserin aut Mingchen Jiang verfasserin aut Junfei Gu verfasserin aut Decai Tang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.944286 kostenfrei https://doaj.org/article/3ff9ed819dce4b81bf79b5a661d1059a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.944286/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
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10.3389/fimmu.2022.944286 doi (DE-627)DOAJ085249610 (DE-599)DOAJ3ff9ed819dce4b81bf79b5a661d1059a DE-627 ger DE-627 rakwb eng RC581-607 Zhongqing Liang verfasserin aut Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. colorectal carcinoma immune-related gene prognostic index (IRGPI) tumor immune microenvironment (TIM) immune-related gene (IRG) immune checkpoint inhibitor (ICI) Immunologic diseases. Allergy Ruolan Sun verfasserin aut Pengcheng Tu verfasserin aut Pengcheng Tu verfasserin aut Yan Liang verfasserin aut Li Liang verfasserin aut Fuyan Liu verfasserin aut Yong Bian verfasserin aut Yong Bian verfasserin aut Gang Yin verfasserin aut Fan Zhao verfasserin aut Mingchen Jiang verfasserin aut Junfei Gu verfasserin aut Decai Tang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.944286 kostenfrei https://doaj.org/article/3ff9ed819dce4b81bf79b5a661d1059a kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.944286/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2022 |
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Zhongqing Liang Ruolan Sun Pengcheng Tu Yan Liang Li Liang Fuyan Liu Yong Bian Gang Yin Fan Zhao Mingchen Jiang Junfei Gu Decai Tang |
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immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma |
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Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma |
abstract |
IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. |
abstractGer |
IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. |
abstract_unstemmed |
IntroductionColorectal cancer shows high incidence and mortality rates. Immune checkpoint blockade can be used to treat colorectal carcinoma (CRC); however, it shows limited effectiveness in most patients.MethodsTo identify patients who may benefit from immunotherapy using immune checkpoint inhibitors, we constructed an immune-related gene prognostic index (IRGPI) for predicting the efficacy of immunotherapy in patients with CRC. Transcriptome datasets and clinical information of patients with CRC were used to identify differential immune-related genes between tumor and para-carcinoma tissue. Using weighted correlation network analysis and Cox regression analysis, the IRGPI was constructed, and Kaplan–Meier analysis was used to evaluate its predictive ability. We also analyzed the molecular and immune characteristics between IRGPI high-and low-risk subgroups, performed sensitivity analysis of ICI treatment, and constructed overall survival-related receiver operating characteristic curves to validate the IRGPI. Finally, IRGPI genes and tumor immune cell infiltration in CRC model mice with orthotopic metastases were analyzed to verify the results.ResultsThe IRGPI was constructed based on the following 11 hub genes: ADIPOQ, CD36, CCL24, INHBE, UCN, IL1RL2, TRIM58, RBCK1, MC1R, PPARGC1A, and LGALS2. Patients with CRC in the high-risk subgroup showed longer overall survival than those in the low-risk subgroup, which was confirmed by GEO database. Clinicopathological features associated with cancer progression significantly differed between the high- and low-risk subgroups. Furthermore, Kaplan–Meier analysis of immune infiltration showed that the increased infiltration of naïve B cells, macrophages M1, and regulatory T cells and reduced infiltration of resting dendritic cells and mast cells led to a worse overall survival in patients with CRC. The ORC curves revealed that IRGPI predicted patient survival more sensitive than the published tumor immune dysfunction and rejection and tumor inflammatory signatureDiscussionThus, the low-risk subgroup is more likely to benefit from ICIs than the high-risk subgroup. CRC model mice showed higher proportions of Tregs, M1 macrophages, M2 macrophages and lower proportions of B cells, memory B cell immune cell infiltration, which is consistent with the IRGPI results. The IRGPI can predict the prognosis of patients with CRC, reflect the CRC immune microenvironment, and distinguish patients who are likely to benefit from ICI therapy. |
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title_short |
Immune-related gene-based prognostic index for predicting survival and immunotherapy outcomes in colorectal carcinoma |
url |
https://doi.org/10.3389/fimmu.2022.944286 https://doaj.org/article/3ff9ed819dce4b81bf79b5a661d1059a https://www.frontiersin.org/articles/10.3389/fimmu.2022.944286/full https://doaj.org/toc/1664-3224 |
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