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BMC Gastroenterology

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Open Access 01-12-2023 | Colon Cancer | Research

APC mutation correlated with poor response of immunotherapy in colon cancer

Authors: Bing Li, Guoliang Zhang, Xuejie Xu

Published in: BMC Gastroenterology | Issue 1/2023

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.

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Title: APC mutation correlated with poor response of immunotherapy in colon cancer
Authors: Bing Li
Guoliang Zhang
Xuejie Xu
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Colon Cancer
Colon Cancer
Published in: BMC Gastroenterology / Issue 1/2023
Electronic ISSN: 1471-230X
DOI: https://doi.org/10.1186/s12876-023-02725-3

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