Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer
Abstract Up to 40% of luminal breast cancer patients carry activating mutations in the PIK3CA gene. PIK3CA mutations commonly co-occur with other mutations, but the implication of this co-occurrence may vary according to the specific genes involved. Here, we characterized a subgroup of luminal breas...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48002-x |
| _version_ | 1797415273561587712 |
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| author | Liat Anabel Sinberger Tamar Zahavi Amir Sonnenblick Mali Salmon‐Divon |
| author_facet | Liat Anabel Sinberger Tamar Zahavi Amir Sonnenblick Mali Salmon‐Divon |
| author_sort | Liat Anabel Sinberger |
| collection | DOAJ |
| description | Abstract Up to 40% of luminal breast cancer patients carry activating mutations in the PIK3CA gene. PIK3CA mutations commonly co-occur with other mutations, but the implication of this co-occurrence may vary according to the specific genes involved. Here, we characterized a subgroup of luminal breast cancer expressing co-mutations in ARID1A and PIK3CA genes and identified their effect on important signaling pathways. Our study included 2609 primary breast cancer samples from the TCGA and METABRIC datasets that were classified based on tumor subtype and the existence of mutations in PIK3CA and ARID1A genes. Differential expression and WGCNA analyses were performed to detect molecular modules affected by the existence of the mutations. Our results reveal various evidence for the involvement of immune-related pathways in luminal tumors harboring ARID1A and PIK3CA mutations, as well as a unique Tumor-infiltrated immune cells composition. We also identified seven key hub genes in the ARID1A-PIK3CA mutated tumors associated with immune-related pathways: CTLA4, PRF1, LCK, CD3E, CD247, ZAP70, and LCP2. Collectively, these results indicate an immune system function that may contribute to tumor survival. Our data induced a hypothesis that ARID1A and PIK3CA mutations' co-occurrence might predict responses to immunotherapy in luminal BC and, if validated, could guide immunotherapy development. |
| first_indexed | 2024-03-09T05:45:19Z |
| format | Article |
| id | doaj.art-ac3e0047997349598d0a0e5f200c4c04 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:45:19Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ac3e0047997349598d0a0e5f200c4c042023-12-03T12:21:44ZengNature PortfolioScientific Reports2045-23222023-11-0113111310.1038/s41598-023-48002-xCoexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancerLiat Anabel Sinberger0Tamar Zahavi1Amir Sonnenblick2Mali Salmon‐Divon3Department of Molecular Biology, Ariel UniversityDepartment of Molecular Biology, Ariel UniversityInstitute of Oncology, Tel Aviv Sourasky Medical CenterDepartment of Molecular Biology, Ariel UniversityAbstract Up to 40% of luminal breast cancer patients carry activating mutations in the PIK3CA gene. PIK3CA mutations commonly co-occur with other mutations, but the implication of this co-occurrence may vary according to the specific genes involved. Here, we characterized a subgroup of luminal breast cancer expressing co-mutations in ARID1A and PIK3CA genes and identified their effect on important signaling pathways. Our study included 2609 primary breast cancer samples from the TCGA and METABRIC datasets that were classified based on tumor subtype and the existence of mutations in PIK3CA and ARID1A genes. Differential expression and WGCNA analyses were performed to detect molecular modules affected by the existence of the mutations. Our results reveal various evidence for the involvement of immune-related pathways in luminal tumors harboring ARID1A and PIK3CA mutations, as well as a unique Tumor-infiltrated immune cells composition. We also identified seven key hub genes in the ARID1A-PIK3CA mutated tumors associated with immune-related pathways: CTLA4, PRF1, LCK, CD3E, CD247, ZAP70, and LCP2. Collectively, these results indicate an immune system function that may contribute to tumor survival. Our data induced a hypothesis that ARID1A and PIK3CA mutations' co-occurrence might predict responses to immunotherapy in luminal BC and, if validated, could guide immunotherapy development.https://doi.org/10.1038/s41598-023-48002-x |
| spellingShingle | Liat Anabel Sinberger Tamar Zahavi Amir Sonnenblick Mali Salmon‐Divon Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer Scientific Reports |
| title | Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer |
| title_full | Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer |
| title_fullStr | Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer |
| title_full_unstemmed | Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer |
| title_short | Coexistent ARID1A-PIK3CA mutations are associated with immune-related pathways in luminal breast cancer |
| title_sort | coexistent arid1a pik3ca mutations are associated with immune related pathways in luminal breast cancer |
| url | https://doi.org/10.1038/s41598-023-48002-x |
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