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基于公共数据集和实验模型,AR与ESR1和PGR的mRNA比率可区分乳腺癌亚型。

mRNA ratios of AR to ESR1 and PGR distinguish breast cancer subtypes based on public datasets and experimental models.

作者信息

Prieto Diego, Rondón-Lagos Milena, Cruz-Tapias Paola, Rincón-Riveros Andrés, Rubiano Wilson, De la Peña Jairo, Vargas Elizabeth, Villegas Victoria E, Rangel Nelson

机构信息

School of Biological Sciences, Universidad Pedagógica y Tecnológica de Colombia, 150003, Tunja, Colombia.

Department of Cardiology, Fundación Cardioinfantil, LaCardio, 1113111, Bogota, Colombia.

出版信息

Sci Rep. 2025 Jul 1;15(1):21793. doi: 10.1038/s41598-025-06856-3.

DOI:10.1038/s41598-025-06856-3
PMID:40593140
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12216603/
Abstract

The role of the androgen receptor (AR) in breast cancer (BC) remains incompletely understood. Here, we conducted a meta-analysis of large-scale microarray transcriptomic datasets to evaluate whether the mRNA expression levels of the androgen receptor gene, relative to those of the estrogen receptor gene (AR/ESR1 ratio) and the progesterone receptor gene (AR/PGR ratio), can help differentiate BC tumor subtypes. Additionally, we used qRT-PCR assays to assess the mRNA levels of the AR/ESR1 and AR/PGR ratios in four cell lines representative of different BC subtypes (MCF7, BT474, MDA-MB453, and MDA-MB231), as well as in breast tissue from a small group of patients (11 cases) stratified by estrogen receptor (ER) status. Our results showed that higher AR gene expression relative to ESR1 and PGR (≥ 2.0 and ≥ 1.54, respectively) were associated with BC patients classified under the Luminal B and HER2-enriched subtypes. Positive values of AR/ESR1 and AR/PGR ratios were also observed in the ER-negative (ER-) cell line MDA-MB453, as well as in tumor tissue from ER- BC patients. Our findings confirm that higher or even positive AR/ESR1 and AR/PGR ratios may be associated with BC cases exhibiting more aggressive clinical and biological features, leading to a worse prognosis.

摘要

雄激素受体(AR)在乳腺癌(BC)中的作用仍未完全明确。在此,我们对大规模微阵列转录组数据集进行了荟萃分析,以评估雄激素受体基因的mRNA表达水平相对于雌激素受体基因(AR/ESR1比值)和孕激素受体基因(AR/PGR比值),是否有助于区分BC肿瘤亚型。此外,我们使用qRT-PCR检测评估了代表不同BC亚型的四种细胞系(MCF7、BT474、MDA-MB453和MDA-MB231)以及一小群按雌激素受体(ER)状态分层的患者(11例)的乳腺组织中AR/ESR1和AR/PGR比值的mRNA水平。我们的结果表明,相对于ESR1和PGR,更高的AR基因表达(分别≥2.0和≥1.54)与归类为Luminal B和HER2富集亚型的BC患者相关。在ER阴性(ER-)细胞系MDA-MB453以及ER-BC患者的肿瘤组织中也观察到AR/ESR1和AR/PGR比值为正值。我们的研究结果证实,更高甚至正值的AR/ESR1和AR/PGR比值可能与表现出更具侵袭性的临床和生物学特征、预后更差的BC病例相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/74333dc589ee/41598_2025_6856_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/933b186a8ee2/41598_2025_6856_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/d7674f0a0320/41598_2025_6856_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/3dea6c2900e8/41598_2025_6856_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/882ab87e295e/41598_2025_6856_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/74333dc589ee/41598_2025_6856_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/933b186a8ee2/41598_2025_6856_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/d7674f0a0320/41598_2025_6856_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/3dea6c2900e8/41598_2025_6856_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/882ab87e295e/41598_2025_6856_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1af/12216603/74333dc589ee/41598_2025_6856_Fig5_HTML.jpg

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本文引用的文献

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Nat Med. 2025 Apr;31(4):1154-1162. doi: 10.1038/s41591-025-03502-3. Epub 2025 Feb 24.
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Breast cancer: pathogenesis and treatments.乳腺癌:发病机制与治疗方法
Signal Transduct Target Ther. 2025 Feb 19;10(1):49. doi: 10.1038/s41392-024-02108-4.
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Androgen receptor expression and clinical significance in breast cancer.雄激素受体在乳腺癌中的表达及临床意义
World J Surg Oncol. 2025 Feb 11;23(1):48. doi: 10.1186/s12957-025-03673-w.
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Looking beyond the ER, PR, and HER2: what's new in the ARsenal for combating breast cancer?超越雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER2):对抗乳腺癌的武器库中有哪些新进展?
Reprod Biol Endocrinol. 2025 Jan 20;23(1):9. doi: 10.1186/s12958-024-01338-z.
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A molecular switch from tumor suppressor to oncogene in ER+ve breast cancer: Role of androgen receptor, JAK-STAT, and lineage plasticity.在 ER+ve 乳腺癌中,一种从肿瘤抑制因子到癌基因的分子开关:雄激素受体、JAK-STAT 和谱系可塑性的作用。
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Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.2022 年全球癌症统计数据:全球 185 个国家和地区 36 种癌症的发病率和死亡率全球估计数。
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