APC mutation correlated with poor response of immunotherapy in colon cancer
Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy e...
Ausführliche Beschreibung
Autor*in: |
Li, Bing [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2023 |
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Anmerkung: |
© The Author(s) 2023 |
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Übergeordnetes Werk: |
Enthalten in: BMC gastroenterology - London : BioMed Central, 2001, 23(2023), 1 vom: 28. März |
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Übergeordnetes Werk: |
volume:23 ; year:2023 ; number:1 ; day:28 ; month:03 |
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DOI / URN: |
10.1186/s12876-023-02725-3 |
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SPR049873741 |
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520 | |a Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. | ||
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10.1186/s12876-023-02725-3 doi (DE-627)SPR049873741 (SPR)s12876-023-02725-3-e DE-627 ger DE-627 rakwb eng Li, Bing verfasserin aut APC mutation correlated with poor response of immunotherapy in colon cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. APC mutation (dpeaa)DE-He213 colon cancer (dpeaa)DE-He213 Tumor mutation burden (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Immune cell infiltration (dpeaa)DE-He213 Zhang, Guoliang aut Xu, Xuejie aut Enthalten in BMC gastroenterology London : BioMed Central, 2001 23(2023), 1 vom: 28. März (DE-627)326643702 (DE-600)2041351-8 1471-230X nnns volume:23 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s12876-023-02725-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 23 2023 1 28 03 |
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10.1186/s12876-023-02725-3 doi (DE-627)SPR049873741 (SPR)s12876-023-02725-3-e DE-627 ger DE-627 rakwb eng Li, Bing verfasserin aut APC mutation correlated with poor response of immunotherapy in colon cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. APC mutation (dpeaa)DE-He213 colon cancer (dpeaa)DE-He213 Tumor mutation burden (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Immune cell infiltration (dpeaa)DE-He213 Zhang, Guoliang aut Xu, Xuejie aut Enthalten in BMC gastroenterology London : BioMed Central, 2001 23(2023), 1 vom: 28. März (DE-627)326643702 (DE-600)2041351-8 1471-230X nnns volume:23 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s12876-023-02725-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 23 2023 1 28 03 |
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10.1186/s12876-023-02725-3 doi (DE-627)SPR049873741 (SPR)s12876-023-02725-3-e DE-627 ger DE-627 rakwb eng Li, Bing verfasserin aut APC mutation correlated with poor response of immunotherapy in colon cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. APC mutation (dpeaa)DE-He213 colon cancer (dpeaa)DE-He213 Tumor mutation burden (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Immune cell infiltration (dpeaa)DE-He213 Zhang, Guoliang aut Xu, Xuejie aut Enthalten in BMC gastroenterology London : BioMed Central, 2001 23(2023), 1 vom: 28. März (DE-627)326643702 (DE-600)2041351-8 1471-230X nnns volume:23 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s12876-023-02725-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 23 2023 1 28 03 |
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10.1186/s12876-023-02725-3 doi (DE-627)SPR049873741 (SPR)s12876-023-02725-3-e DE-627 ger DE-627 rakwb eng Li, Bing verfasserin aut APC mutation correlated with poor response of immunotherapy in colon cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. APC mutation (dpeaa)DE-He213 colon cancer (dpeaa)DE-He213 Tumor mutation burden (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Immune cell infiltration (dpeaa)DE-He213 Zhang, Guoliang aut Xu, Xuejie aut Enthalten in BMC gastroenterology London : BioMed Central, 2001 23(2023), 1 vom: 28. März (DE-627)326643702 (DE-600)2041351-8 1471-230X nnns volume:23 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s12876-023-02725-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 23 2023 1 28 03 |
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10.1186/s12876-023-02725-3 doi (DE-627)SPR049873741 (SPR)s12876-023-02725-3-e DE-627 ger DE-627 rakwb eng Li, Bing verfasserin aut APC mutation correlated with poor response of immunotherapy in colon cancer 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. APC mutation (dpeaa)DE-He213 colon cancer (dpeaa)DE-He213 Tumor mutation burden (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Immune cell infiltration (dpeaa)DE-He213 Zhang, Guoliang aut Xu, Xuejie aut Enthalten in BMC gastroenterology London : BioMed Central, 2001 23(2023), 1 vom: 28. März (DE-627)326643702 (DE-600)2041351-8 1471-230X nnns volume:23 year:2023 number:1 day:28 month:03 https://dx.doi.org/10.1186/s12876-023-02725-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 23 2023 1 28 03 |
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APC mutation correlated with poor response of immunotherapy in colon cancer |
abstract |
Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. © The Author(s) 2023 |
abstractGer |
Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. © The Author(s) 2023 |
abstract_unstemmed |
Objective APC (adenomatous polyposis coli) gene mutation is a central initialization in colon cancer tumorigenesis. However, the connection between APC gene mutation and immunotherapy efficacy for colon cancer remains unknown. This study aimed to explore the impact of APC mutation on immunotherapy efficacy for colon cancer. Methods Colon cancer data from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) were used for the combined analysis. Survival analysis was performed to evaluate the association between APC mutation and immunotherapy efficacy in colon cancer patients. The expressions of immune check point molecules, tumor mutation burden (TMB), CpG methylation level, tumor purity (TP), microsatellite instability (MSI) status and tumor-infiltrating lymphocyte (TIL) in the two APC status were compared to evaluate the associations between APC mutation and immunotherapy efficacy indicators. Gene set enrichment analysis (GSEA) was performed to identify signaling pathways related to APC mutation. Results APC was the most frequently mutated gene in colon cancer. The survival analysis demonstrated that APC mutation was correlated with a worse immunotherapy outcome. APC mutation was associated with lower TMB, lower expression of immune check point molecules (PD-1/PD-L1/PD-L2), higher TP, lower MSI-High proportion and less CD8 + T cells and follicular helper T cells infiltration. GSEA indicated that APC mutation up-regulated mismatch repair pathway, which may play a negative role in evoking an antitumor immune response. Conclusion APC mutation is associated with worse immunotherapy outcome and inhibition of antitumor immunity. It can be used as a negative biomarker to predict immunotherapy response. © The Author(s) 2023 |
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APC mutation correlated with poor response of immunotherapy in colon cancer |
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https://dx.doi.org/10.1186/s12876-023-02725-3 |
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Zhang, Guoliang Xu, Xuejie |
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