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Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer
To date, anticancer immunotherapy has presented some clinical benefits to most of advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients. In addition to MSI status, we aimed to reveal the potential predictive value of adenomatous polyposis...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300385/ https://www.ncbi.nlm.nih.gov/pubmed/35874638 http://dx.doi.org/10.1155/2022/6567998 |
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author | Feng, Fen Sun, Huake Zhao, Zhikun Sun, Chao Zhao, Yongtian Lin, Hanqing Yang, Jie Xiao, Yajie Wang, Wei Wu, Dongfang |
author_facet | Feng, Fen Sun, Huake Zhao, Zhikun Sun, Chao Zhao, Yongtian Lin, Hanqing Yang, Jie Xiao, Yajie Wang, Wei Wu, Dongfang |
author_sort | Feng, Fen |
collection | PubMed |
description | To date, anticancer immunotherapy has presented some clinical benefits to most of advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients. In addition to MSI status, we aimed to reveal the potential predictive value of adenomatous polyposis coli (APC) gene mutations in CRC patients. A total of 238 Chinese CRC patients was retrospectively identified and analyzed for clinical features and gene alternations in APC-mutant type (MT) and APC-wild-type (WT) groups. Clinical responses were then evaluated from the public TCGA database and MSKCC immunotherapy database. Although programmed cell death ligand 1 (PD-L1) level, MSI status, loss of heterogeneity at the human leukocyte antigen (HLA LOH), and tumor neoantigen burden (TNB) level were not statistically different between the APC-MT group and APC-WT group, tumor mutation burden (TMB) level was significantly higher in APC-MT patients (P < 0.05). Furthermore, comutation analysis for APC mutations revealed co-occurring genomic alterations of PCDHB7 and exclusive mutations of CTNNB1, BRAF, AFF3, and SNX25 (P < 0.05). Besides, overall survival from MSKCC-CRC cohort was longer in the APC-WT group than in the APC-MT group (HR 2.26 (95% CI 1.05–4.88), P < 0.05). Furthermore, most of patients in the APC-WT group were detected as high-grade immune subtypes (C2–C4) comparing with those in the APC-MT group. In addition, the percentages of NK T cells, Treg cells, and fibroblasts cells were higher in APC-WT patients than in APC-MT patients (P < 0.05). In summary, APC mutations might be associated with poor outcomes for immunotherapy in CRC patients regardless of MSI status. This study suggested APC gene mutations might be a potential predictor for immunotherapy in CRC. |
format | Online Article Text |
id | pubmed-9300385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-93003852022-07-21 Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer Feng, Fen Sun, Huake Zhao, Zhikun Sun, Chao Zhao, Yongtian Lin, Hanqing Yang, Jie Xiao, Yajie Wang, Wei Wu, Dongfang J Oncol Research Article To date, anticancer immunotherapy has presented some clinical benefits to most of advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients. In addition to MSI status, we aimed to reveal the potential predictive value of adenomatous polyposis coli (APC) gene mutations in CRC patients. A total of 238 Chinese CRC patients was retrospectively identified and analyzed for clinical features and gene alternations in APC-mutant type (MT) and APC-wild-type (WT) groups. Clinical responses were then evaluated from the public TCGA database and MSKCC immunotherapy database. Although programmed cell death ligand 1 (PD-L1) level, MSI status, loss of heterogeneity at the human leukocyte antigen (HLA LOH), and tumor neoantigen burden (TNB) level were not statistically different between the APC-MT group and APC-WT group, tumor mutation burden (TMB) level was significantly higher in APC-MT patients (P < 0.05). Furthermore, comutation analysis for APC mutations revealed co-occurring genomic alterations of PCDHB7 and exclusive mutations of CTNNB1, BRAF, AFF3, and SNX25 (P < 0.05). Besides, overall survival from MSKCC-CRC cohort was longer in the APC-WT group than in the APC-MT group (HR 2.26 (95% CI 1.05–4.88), P < 0.05). Furthermore, most of patients in the APC-WT group were detected as high-grade immune subtypes (C2–C4) comparing with those in the APC-MT group. In addition, the percentages of NK T cells, Treg cells, and fibroblasts cells were higher in APC-WT patients than in APC-MT patients (P < 0.05). In summary, APC mutations might be associated with poor outcomes for immunotherapy in CRC patients regardless of MSI status. This study suggested APC gene mutations might be a potential predictor for immunotherapy in CRC. Hindawi 2022-07-13 /pmc/articles/PMC9300385/ /pubmed/35874638 http://dx.doi.org/10.1155/2022/6567998 Text en Copyright © 2022 Fen Feng et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Feng, Fen Sun, Huake Zhao, Zhikun Sun, Chao Zhao, Yongtian Lin, Hanqing Yang, Jie Xiao, Yajie Wang, Wei Wu, Dongfang Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer |
title | Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer |
title_full | Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer |
title_fullStr | Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer |
title_full_unstemmed | Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer |
title_short | Identification of APC Mutation as a Potential Predictor for Immunotherapy in Colorectal Cancer |
title_sort | identification of apc mutation as a potential predictor for immunotherapy in colorectal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300385/ https://www.ncbi.nlm.nih.gov/pubmed/35874638 http://dx.doi.org/10.1155/2022/6567998 |
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