Department of Biosciences, COMSATS University, Islamabad, Pakistan.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Olympic-Ro 43Gil 88, Songpa-Gu, Seoul, Republic of Korea.
J Transl Med. 2018 Dec 28;16(1):374. doi: 10.1186/s12967-018-1743-9.
The clinical significance of fibroblast growth factor receptor 1 (FGFR1) protein expression in pancreatic cancer is largely unknown. In this study, we aimed investigate the clinical significance of FGFR1 expression in pancreatic cancer.
First, we investigated the relationship between FGFR pathway gene expression and clinicopathological data in three pancreatic cancer cohorts containing 313 cases. Subsequently, to confirm the findings from the discovery cohorts, we performed immunohistochemistry (IHC) of FGFR1 protein in a validation cohort of 205 pancreatic cancer cases.
In discovery cohort 1, FGFR1 and Klotho beta (KLB) overexpression was associated with low tumor stage (P < 0.05), low tumor grade (P < 0.05), and better overall survival. Multivariate analysis predicted FGFR1 (P < 0.05) as a prognostic factor for better overall survival. In discovery cohorts 2 and 3, only FGFR1 overexpression was associated with better overall survival (P < 0.05). In the validation cohort, there were 15.7% and 61% strong and weak/moderate FGFR1-positive cases, respectively. FGFR1-positive cases showed better overall survival than FGFR1-negative cases (P < 0.05). Furthermore, multivariate analysis revealed FGFR1 positivity as an independent prognostic factor for better overall survival in pancreatic cancer patients (hazard ratio 0.677, 95% confidence interval 0.471-0.972, P = 0.035).
FGFR1 expression, as estimated by IHC, may be used to define clinically distinct subtypes in pancreatic cancer. Moreover, FGFR1-based subclassification of pancreatic cancer may lead to new therapeutic approaches for the FGFR1-positive subtype.
成纤维细胞生长因子受体 1（FGFR1）蛋白在胰腺癌中的表达的临床意义在很大程度上尚不清楚。在本研究中，我们旨在研究 FGFR1 表达在胰腺癌中的临床意义。
首先，我们研究了三个包含 313 例病例的胰腺癌队列中 FGFR 通路基因表达与临床病理数据之间的关系。随后，为了确认发现队列的结果，我们对 205 例胰腺癌病例的验证队列进行了 FGFR1 蛋白免疫组织化学（IHC）检测。
在发现队列 1 中，FGFR1 和 Klotho beta（KLB）过表达与低肿瘤分期（P<0.05）、低肿瘤分级（P<0.05）和更好的总生存期相关。多变量分析预测 FGFR1（P<0.05）是总生存期更好的预后因素。在发现队列 2 和 3 中，仅 FGFR1 过表达与更好的总生存期相关（P<0.05）。在验证队列中，分别有 15.7%和 61%的病例为 FGFR1 强阳性和弱阳性/中度阳性。FGFR1 阳性病例的总生存期优于 FGFR1 阴性病例（P<0.05）。此外，多变量分析显示 FGFR1 阳性是胰腺癌患者总生存期更好的独立预后因素（危险比 0.677，95%置信区间 0.471-0.972，P=0.035）。
通过 IHC 估计的 FGFR1 表达可能用于定义胰腺癌中的临床显著亚型。此外，基于 FGFR1 的胰腺癌亚分类可能为 FGFR1 阳性亚型带来新的治疗方法。
