Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer.
Fibroblast growth factor receptor-1 protein expression is associated with prognosis in estrogen receptor-positive/human epidermal growth factor receptor-2-negative primary breast cancer.
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DOI：
10.1111/cas.12897
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发表时间：
2016-04
期刊：
影响因子：
5.7
通讯作者：
Iwase H
中科院分区：
文献类型：
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作者：
Tomiguchi M;Yamamoto Y;Yamamoto-Ibusuki M;Goto-Yamaguchi L;Fujiki Y;Fujiwara S;Sueta A;Hayashi M;Takeshita T;Inao T;Iwase H
最近，对新靶向疗法开发的研究集中在特定的遗传改变上，以创造先进的、更个性化的治疗。据报道，其中一个靶基因成纤维细胞生长因子受体-1（FGFR 1）在雌激素受体（ER）阳性亚型乳腺癌中扩增，并被认为是通过ER和生长因子受体信号传导之间的串扰而产生内分泌抵抗的一种可能机制。我们在基因拷贝数、转录本和蛋白表达水平上对FGFR 1进行了全面分析，并检查了FGFR 1状态与临床病理参数之间的关系，包括在我们研究所接受标准治疗的307例ER阳性/HER 2阴性原发性乳腺癌患者的预后。最值得注意的是，在85例患者（27.7%）中观察到高水平的FGFR 1蛋白表达，并且与浸润性肿瘤大小呈正相关（P = 0.039）。此外，单变量分析显示，高FGFR 1蛋白表达与低无复发生存率显著相关（P = 0.0019，HR：2.63，95%置信区间：1.17-5.98），并且如果观察期延长至标准内分泌治疗期的5年以上，则显示复发事件增加的趋势。43例（14.0%）患者发现FGFR 1获得/扩增，仅与较高的核分级相关（P = 0.010）。FGFR 1 mRNA表达水平与临床病理因素无相关性。总体而言，FGFR 1蛋白表达水平可能是ER阳性/HER 2阴性原发性乳腺癌的生物标志物，可能对标准治疗产生耐药性，并且可能是识别更特定患者的有用工具，这些患者将从FGFR-1靶向治疗中获益。
Recently, research into the development of new targeted therapies has focused on specific genetic alterations to create advanced, more personalized treatment. One of the target genes, fibroblast growth factor receptor‐1 (FGFR1), has been reported to be amplified in estrogen receptor (ER)‐positive subtype breast cancer, and is considered one possible mechanism of endocrine resistance through cross‐talk between ER and growth factor receptor signaling. We performed a comprehensive analysis of FGFR1 at the levels of gene copy number, transcript and protein expression, and examined the relationships between FGFR1 status and clinicopathological parameters, including prognosis in 307 ER‐positive/HER2‐negative primary breast cancer patients treated with standard care at our institute. Most notably, a high level of FGFR1 protein expression was observed in 85 patients (27.7%), and was positively associated with invasive tumor size (P = 0.039). Furthermore, univariate analysis revealed that high FGFR1 protein expression was significantly correlated with poor relapse‐free survival rate (P = 0.0019, HR: 2.63, 95% confidence interval: 1.17–5.98), and showed a tendency towards an increase in recurrent events if the observation period extended beyond the 5 years of the standard endocrine treatment term. FGFR1 gain/amplification was found in 43 (14.0%) patients, which was only associated with higher nuclear grade (P = 0.010). No correlation was found between FGFR1 mRNA expression levels and any clinicopathological factors. Overall, the level of FGFR1 protein expression may be a biomarker of ER‐positive/HER2‐negative primary breast cancer with possible resistance to standard treatment, and may be a useful tool to identify more specific patients who would benefit from FGFR‐1 targeted therapy.