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 immuno...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-023-02725-3 |
| _version_ | 1797853766058246144 |
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| author | Bing Li Guoliang Zhang Xuejie Xu |
| author_facet | Bing Li Guoliang Zhang Xuejie Xu |
| author_sort | Bing Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T19:54:56Z |
| format | Article |
| id | doaj.art-184f4932c4094d36ad6a84e368613869 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-04-09T19:54:56Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-184f4932c4094d36ad6a84e3686138692023-04-03T05:29:08ZengBMCBMC Gastroenterology1471-230X2023-03-0123111010.1186/s12876-023-02725-3APC mutation correlated with poor response of immunotherapy in colon cancerBing Li0Guoliang Zhang1Xuejie Xu2Department of Medical Oncology, The Affiliated Hospital of Putian UniversityDepartment of Thyroid Surgery, The Affiliated Hospital of Putian UniversityDepartment of Medical Oncology, The Affiliated Hospital of Putian UniversityAbstract 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.https://doi.org/10.1186/s12876-023-02725-3APC mutationcolon cancerTumor mutation burdenImmunotherapyImmune cell infiltration |
| spellingShingle | Bing Li Guoliang Zhang Xuejie Xu APC mutation correlated with poor response of immunotherapy in colon cancer BMC Gastroenterology APC mutation colon cancer Tumor mutation burden Immunotherapy Immune cell infiltration |
| title | APC mutation correlated with poor response of immunotherapy in colon cancer |
| title_full | APC mutation correlated with poor response of immunotherapy in colon cancer |
| title_fullStr | APC mutation correlated with poor response of immunotherapy in colon cancer |
| title_full_unstemmed | APC mutation correlated with poor response of immunotherapy in colon cancer |
| title_short | APC mutation correlated with poor response of immunotherapy in colon cancer |
| title_sort | apc mutation correlated with poor response of immunotherapy in colon cancer |
| topic | APC mutation colon cancer Tumor mutation burden Immunotherapy Immune cell infiltration |
| url | https://doi.org/10.1186/s12876-023-02725-3 |
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