High FGFR4 protein expression, but not FGFR1 or FGFR2, predicts poor prognosis in pancreatic ductal adenocarcinoma.

IF 3.4 2区 医学 Q2 ONCOLOGY
Marcin Braun, Justyna Durślewicz, Julia Sołek, Zuzanna Nowicka, Aleksandra Zielińska, Paulina Antosik, Dariusz Grzanka
{"title":"High FGFR4 protein expression, but not FGFR1 or FGFR2, predicts poor prognosis in pancreatic ductal adenocarcinoma.","authors":"Marcin Braun, Justyna Durślewicz, Julia Sołek, Zuzanna Nowicka, Aleksandra Zielińska, Paulina Antosik, Dariusz Grzanka","doi":"10.1186/s12885-025-14976-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The number of prognostic and predictive factors for pancreatic ductal adenocarcinoma (PDAC) is limited. Fibroblast growth factor receptors (FGFRs) are emerging as potential therapeutic targets, especially in cases with FGFR2 gene fusions. However, the prognostic relevance of FGFR1, FGFR2, and FGFR4 protein expression in PDAC remains unclear.</p><p><strong>Methods: </strong>Immunohistochemical analysis of FGFR1, FGFR2, and FGFR4 was performed on 99 PDAC and 60 adjacent normal pancreatic tissue samples. Protein expression was quantified using the H-score method and correlated with clinicopathological variables and survival. Publicly available datasets from the GEO repository and the cancer genome atlas (TCGA) were used for pathway enrichment analysis and validation of findings at the mRNA level.</p><p><strong>Results: </strong>FGFR2 and FGFR4 showed differential expression between tumor and normal tissues, while FGFR1 did not. High FGFR4 protein expression was significantly associated with shorter disease-free survival (DFS) in both univariable and multivariable analyses. FGFR2 high expression cases showed a trend towards poor DFS, while FGFR1 had no prognostic impact. In silico analysis confirmed that high FGFR4 mRNA levels are associated with worse DFS. Co-expression and enrichment analysis linked FGFR4 overexpression with developmental, metabolic, and stemness-related processes.</p><p><strong>Conclusion: </strong>FGFR4 showed the strongest prognostic association among the FGFR family members studied, with high protein expression correlating with shorter disease-free survival in PDAC patients. These findings underscore the potential of FGFR4 as a biomarker for recurrence risk, while also highlighting the complexity of FGFR-related signaling and its context-dependent clinical relevance.</p>","PeriodicalId":9131,"journal":{"name":"BMC Cancer","volume":"25 1","pages":"1519"},"PeriodicalIF":3.4000,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12885-025-14976-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: The number of prognostic and predictive factors for pancreatic ductal adenocarcinoma (PDAC) is limited. Fibroblast growth factor receptors (FGFRs) are emerging as potential therapeutic targets, especially in cases with FGFR2 gene fusions. However, the prognostic relevance of FGFR1, FGFR2, and FGFR4 protein expression in PDAC remains unclear.

Methods: Immunohistochemical analysis of FGFR1, FGFR2, and FGFR4 was performed on 99 PDAC and 60 adjacent normal pancreatic tissue samples. Protein expression was quantified using the H-score method and correlated with clinicopathological variables and survival. Publicly available datasets from the GEO repository and the cancer genome atlas (TCGA) were used for pathway enrichment analysis and validation of findings at the mRNA level.

Results: FGFR2 and FGFR4 showed differential expression between tumor and normal tissues, while FGFR1 did not. High FGFR4 protein expression was significantly associated with shorter disease-free survival (DFS) in both univariable and multivariable analyses. FGFR2 high expression cases showed a trend towards poor DFS, while FGFR1 had no prognostic impact. In silico analysis confirmed that high FGFR4 mRNA levels are associated with worse DFS. Co-expression and enrichment analysis linked FGFR4 overexpression with developmental, metabolic, and stemness-related processes.

Conclusion: FGFR4 showed the strongest prognostic association among the FGFR family members studied, with high protein expression correlating with shorter disease-free survival in PDAC patients. These findings underscore the potential of FGFR4 as a biomarker for recurrence risk, while also highlighting the complexity of FGFR-related signaling and its context-dependent clinical relevance.

高FGFR4蛋白表达,而不是FGFR1或FGFR2,预测胰腺导管腺癌的不良预后。
背景:胰腺导管腺癌(PDAC)的预后和预测因素数量有限。成纤维细胞生长因子受体(FGFRs)正在成为潜在的治疗靶点,特别是在FGFR2基因融合的病例中。然而,FGFR1、FGFR2和FGFR4蛋白在PDAC中的表达与预后的相关性尚不清楚。方法:对99例PDAC和60例相邻正常胰腺组织样本进行FGFR1、FGFR2和FGFR4的免疫组化分析。采用H-score法定量蛋白表达,并与临床病理变量和生存率相关。来自GEO知识库和癌症基因组图谱(TCGA)的公开可用数据集用于mRNA水平的途径富集分析和结果验证。结果:FGFR2和FGFR4在肿瘤组织和正常组织中存在差异表达,而FGFR1无差异表达。在单变量和多变量分析中,高FGFR4蛋白表达与较短的无病生存期(DFS)显著相关。FGFR2高表达病例表现出较差的DFS趋势,而FGFR1对预后没有影响。计算机分析证实,高FGFR4 mRNA水平与较差的DFS相关。共表达和富集分析将FGFR4过表达与发育、代谢和干细胞相关过程联系起来。结论:FGFR4在FGFR家族成员中表现出最强的预后相关性,在PDAC患者中,高蛋白表达与较短的无病生存期相关。这些发现强调了FGFR4作为复发风险生物标志物的潜力,同时也强调了fgfr相关信号的复杂性及其依赖于环境的临床相关性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信