PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■乳房X线摄影乳腺密度（MBD）是确定的乳腺癌风险因素，然而，潜在的分子机制仍有待破译。成纤维细胞生长因子受体1(FGFR1)扩增与乳腺癌发展和在与高乳房X线摄影密度和乳腺癌微环境相关的生物过程中发现的异常FGF信号相关。这项研究的目的是研究来自同一患者的成对的肿瘤旁组织和肿瘤组织之间的FGF/FGFR1表达。及其与MBD和肿瘤特征的关系。
■通过免疫组织化学分析了参加Karolinska乳房X线摄影项目乳腺癌风险预测（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327名患者的RNA测序数据获得。
■FGFR1水平在肿瘤旁组织和肿瘤组织中表达不同，在58%的肿瘤中检测到FGFR1水平升高。FGFR1在肿瘤组织中的高表达与较差的肿瘤特征相关；高组织学分级（OR=1.86，95％CI1.00-3.44），高Ki67增殖指数（OR=2.18，95％CI1.18-4.02）以及管腔B样亚型肿瘤（OR=2.56，95CI1.29-5.06）。虽然FGFR1表达与MBD之间没有明确的关联，FGF配体(FGF1、FGF11、FGF18)表达与MBD呈正相干。
■放在一起，这些发现支持FGF/FGFR1系统在早期乳腺癌中的作用,值得在MBD-乳腺癌背景下进一步研究.
■通过免疫组织化学分析了参加Karolinska乳房X线摄影项目乳腺癌风险预测（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327名患者的RNA测序数据获得。
■FGFR1水平在肿瘤旁组织和肿瘤组织中表达不同，在58%的肿瘤中检测到FGFR1水平升高。FGFR1在肿瘤组织中的高表达与较差的肿瘤特征相关；高组织学分级（OR=1.86，95％CI1.00-3.44），高Ki67增殖指数（OR=2.18，95％CI1.18-4.02）以及管腔B样亚型肿瘤（OR=2.56，95CI1.29-5.06）。虽然FGFR1表达与MBD之间没有明确的关联，FGF配体(FGF1、FGF11、FGF18)表达与MBD呈正相干。
■放在一起，这些发现支持FGF/FGFR1系统在早期乳腺癌中的作用,值得在MBD-乳腺癌背景下进一步研究.
