Liver tropism of ER mutant breast cancer is characterized by unique molecular changes and immune infiltration.

Autor: Wu Y; School of Medicine, Tsinghua University, Beijing, China.; Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, Pittsburgh, PA, USA., Li Z; Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, Pittsburgh, PA, USA.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Lee AV; Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, Pittsburgh, PA, USA.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Institute for Precision Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Oesterreich S; Women's Cancer Research Center, UPMC Hillman Cancer Center, Magee-Womens Research Institute, Pittsburgh, PA, USA.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Luo B; Department of General Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China. luobin@mail.tsinghua.edu.cn.
Jazyk: angličtina
Zdroj: Breast cancer research and treatment [Breast Cancer Res Treat] 2024 Jun; Vol. 205 (2), pp. 371-386. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1007/s10549-024-07255-4
Abstrakt: Purpose: Hotspot estrogen receptor alpha (ER/ESR1) mutations are recognized as the driver for both endocrine resistance and metastasis in advanced ER-positive (ER+) breast cancer, but their contributions to metastatic organ tropism remain insufficiently understood. In this study, we aim to comprehensively profile the organotropic metastatic pattern for ESR1 mutant breast cancer.
Methods: The organ-specific metastatic pattern of ESR1 mutant breast cancer was delineated using multi-omics data from multiple publicly available cohorts of ER+ metastatic breast cancer patients. Gene mutation/copy number variation (CNV) and differential gene expression analyses were performed to identify the genomic and transcriptomic alterations uniquely associated with ESR1 mutant liver metastasis. Upstream regulator, downstream pathway, and immune infiltration analysis were conducted for subsequent mechanistic investigations.
Results: ESR1 mutation-driven liver tropism was revealed by significant differences, encompassing a higher prevalence of liver metastasis in patients with ESR1 mutant breast cancer and an enrichment of mutations in liver metastatic samples. The significant enrichment of AGO2 copy number amplifications (CNAs) and multiple gene expression changes were revealed uniquely in ESR1 mutant liver metastasis. We also unveiled alterations in downstream signaling pathways and immune infiltration, particularly an enrichment of neutrophils, suggesting potential therapeutic vulnerabilities.
Conclusion: Our data provide a comprehensive characterization of the behaviors and mechanisms of ESR1 mutant liver metastasis, paving the way for the development of personalized therapy to target liver metastasis for patients with ESR1 mutant breast cancer.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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