Boraka Öykü, Klintman Marie, Vallon-Christersson Johan, Zackrisson Sophia, Hall Per, Borgquist Signe, Rosendahl Ann H
Department of Clinical Sciences Lund, Oncology, Lund University, Skåne University Hospital, Lund, Sweden.
Department of Clinical Sciences Lund, Oncology, Lund University, Lund, Sweden.
Front Oncol. 2023 Jul 20;13:1230821. doi: 10.3389/fonc.2023.1230821. eCollection 2023.
Mammographic breast density (MBD) is an established breast cancer risk factor, yet the underlying molecular mechanisms remain to be deciphered. Fibroblast growth factor receptor 1 (FGFR1) amplification is associated with breast cancer development and aberrant FGF signaling found in the biological processes related to both high mammographic density and breast cancer microenvironment. The aim of this study was to investigate the FGF/FGFR1 expression in-between paired tumor-adjacent and tumor tissues from the same patient, and its associations with MBD and tumor characteristics.
FGFR1 expression in paired tissues from 426 breast cancer patients participating in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohort study was analyzed by immunohistochemistry. FGF ligand expression was obtained from RNA-sequencing data for 327 of the included patients.
FGFR1 levels were differently expressed in tumor-adjacent and tumor tissues, with increased FGFR1 levels detected in 58% of the tumors. High FGFR1 expression in tumor tissues was associated with less favorable tumor characteristics; high histological grade (OR=1.86, 95% CI 1.00-3.44), high Ki67 proliferative index (OR=2.18, 95% CI 1.18-4.02) as well as tumors of Luminal B-like subtype (OR=2.56, 95%CI 1.29-5.06). While no clear association between FGFR1 expression and MBD was found, FGF ligand (FGF1, FGF11, FGF18) expression was positively correlated with MBD.
Taken together, these findings support a role of the FGF/FGFR1 system in early breast cancer which warrants further investigation in the MBD-breast cancer context.
乳腺钼靶密度（MBD）是一种已确定的乳腺癌风险因素，但其潜在的分子机制仍有待阐明。成纤维细胞生长因子受体1（FGFR1）扩增与乳腺癌发展相关，且在与高乳腺钼靶密度和乳腺癌微环境相关的生物学过程中发现了异常的FGF信号传导。本研究的目的是调查来自同一患者的配对肿瘤旁组织和肿瘤组织之间的FGF/FGFR1表达，及其与MBD和肿瘤特征的关联。
通过免疫组织化学分析了参与卡罗林斯卡乳腺钼靶乳腺癌风险预测项目（KARMA）队列研究的426例乳腺癌患者配对组织中的FGFR1表达。FGF配体表达从纳入的327例患者的RNA测序数据中获得。
FGFR1水平在肿瘤旁组织和肿瘤组织中表达不同，58%的肿瘤中检测到FGFR1水平升高。肿瘤组织中高FGFR1表达与较差的肿瘤特征相关；高组织学分级（OR=1.86，95%CI 1.00-3.44）、高Ki67增殖指数（OR=2.18，95%CI 1.18-4.02）以及Luminal B样亚型肿瘤（OR=2.56，95%CI 1.29-5.06）。虽然未发现FGFR1表达与MBD之间存在明确关联，但FGF配体（FGF1、FGF11、FGF18）表达与MBD呈正相关。
综上所述，这些发现支持FGF/FGFR1系统在早期乳腺癌中的作用，这值得在MBD-乳腺癌背景下进一步研究。
