Author:
Anabel Sinberger Liat,Zahavi Tamar,Sonnenblick Amir,Salmon‐Divon Mali
Abstract
AbstractUp 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.
Funder
Israel Science Foundation
Israel Cancer Association
Ministry of Health, State of Israel
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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