Fibroblast Growth Factor Receptor 4 As a Prognostic Indicator in Triple-negative Breast Cancer

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2022 Feb 4

PMID 35117296

Authors

Wei Wei

Shiyu Cao

Jing Liu

Yuhang Wang

Quanfu Song

Leha A

Shanshan Sun

Xianyu Zhang

Xiaoshuan Liang

Yongdong Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Triple-negative breast cancer (TNBC) constitutes up to 15% of all breast cancers. It is one of the most aggressive breast cancers and is more prone to metastasize compared with other subtypes. Breast cancer patients with this subtype usually have a poor prognosis. Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and early analyses identified that FGFR4 was involved in breast cancer. However, the prognostic effect of FGFR4 on TNBC is unknown. In the present study, we investigated the association between FGFR4 and TNBC prognosis.

Methods: A total of 282 TNBC patients were enrolled. FGFR4 protein expression was detected in these 282 TNBC patients using immunohistochemistry (IHC).

Results: In the present study, FGFR4 was highly expressed in TNBC patients. Lymph node metastasis (LNM) (P=0.033) and p53 status (P=0.019) were associated with high FGFR4 expression. Univariate analysis identified high FGFR4 expression (P=0.016) as a prognostic predictor, and multivariate analysis found that high FGFR4 expression (P=0.016) was an independent prognostic factor. The Kaplan-Meier survival curve showed that high FGFR4 protein expression was correlated with poorer overall survival (OS).

Conclusions: The results of our present study show that FGFR4 protein expression is correlated with a worse prognosis in TNBC.

Citing Articles

Identification of transcription factors associated with the disease-free survival of triple-negative breast cancer through weighted gene co-expression network analysis.

Wang H, Hao R, Liu W, Zhang Y, Ma S, Lu Y Cytojournal. 2025; 21:71.

PMID: 39917004 PMC: 11801659. DOI: 10.25259/Cytojournal_127_2024.

Transcriptomic Analysis of Subtype-Specific Tyrosine Kinases as Triple Negative Breast Cancer Biomarkers.

Limsakul P, Choochuen P, Charupanit G, Charupanit K Cancers (Basel). 2023; 15(2).

PMID: 36672350 PMC: 9856281. DOI: 10.3390/cancers15020403.

FGFR1-4 RNA-Based Gene Alteration and Expression Analysis in Squamous Non-Small Cell Lung Cancer.

Moes-Sosnowska J, Skupinska M, Lechowicz U, Szczepulska-Wojcik E, Skronska P, Rozy A Int J Mol Sci. 2022; 23(18).

PMID: 36142417 PMC: 9505002. DOI: 10.3390/ijms231810506.

Focal pyroptosis-related genes and are prognostic markers for triple-negative breast cancer with brain metastases.

Huang Q, Fang D, Nong B, Zeng J Transl Cancer Res. 2022; 10(11):4845-4858.

PMID: 35116337 PMC: 8797367. DOI: 10.21037/tcr-21-2182.

petroleum ether extract reverses the resistance of triple-negative breast cancer to docetaxel via pregnane X receptor.

Qiao E, Yang H, Yu X, Gong L, Zhang X, Chen D Ann Transl Med. 2021; 9(17):1389.

PMID: 34733941 PMC: 8506551. DOI: 10.21037/atm-21-4199.

References

Yu C, Wang F, Kan M, Jin C, Jones R, Weinstein M . Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4. J Biol Chem. 2000; 275(20):15482-9. DOI: 10.1074/jbc.275.20.15482. View

Katoh M, Nakagama H . FGF receptors: cancer biology and therapeutics. Med Res Rev. 2013; 34(2):280-300. DOI: 10.1002/med.21288. View

Dumay A, Feugeas J, Wittmer E, Lehmann-Che J, Bertheau P, Espie M . Distinct tumor protein p53 mutants in breast cancer subgroups. Int J Cancer. 2012; 132(5):1227-31. DOI: 10.1002/ijc.27767. View

. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418):61-70. PMC: 3465532. DOI: 10.1038/nature11412. View

Li Y, Xu J, Zhu G, Huang Z, Lu Y, Li X . Apigenin suppresses the stem cell-like properties of triple-negative breast cancer cells by inhibiting YAP/TAZ activity. Cell Death Discov. 2018; 4:105. PMC: 6244166. DOI: 10.1038/s41420-018-0124-8. View

Metzger-Filho O, Tutt A, de Azambuja E, Saini K, Viale G, Loi S . Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol. 2012; 30(15):1879-87. DOI: 10.1200/JCO.2011.38.2010. View

Jiang Y, Sun S, Wei W, Ren Y, Liu J, Pang D . Association of FGFR3 and FGFR4 gene polymorphisms with breast cancer in Chinese women of Heilongjiang province. Oncotarget. 2015; 6(32):34023-9. PMC: 4741823. DOI: 10.18632/oncotarget.5850. View

Thisse B, Thisse C . Functions and regulations of fibroblast growth factor signaling during embryonic development. Dev Biol. 2005; 287(2):390-402. DOI: 10.1016/j.ydbio.2005.09.011. View

Zhao X, Xu F, Dominguez N, Xiong Y, Xiong Z, Peng H . FGFR4 provides the conduit to facilitate FGF19 signaling in breast cancer progression. Mol Carcinog. 2018; 57(11):1616-1625. DOI: 10.1002/mc.22884. View

10.

Hsu C, Ho D, Yang C, Lai C, Yu I, Chiang H . Interobserver reproducibility of Her-2/neu protein overexpression in invasive breast carcinoma using the DAKO HercepTest. Am J Clin Pathol. 2002; 118(5):693-8. DOI: 10.1309/6ANB-QXCF-EHKC-7UC7. View

11.

Wei W, You Z, Sun S, Wang Y, Zhang X, Pang D . Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer. Mol Carcinog. 2018; 57(8):988-996. DOI: 10.1002/mc.22819. View

12.

Giannakakou P, Poy G, Zhan Z, Knutsen T, Blagosklonny M, Fojo T . Paclitaxel selects for mutant or pseudo-null p53 in drug resistance associated with tubulin mutations in human cancer. Oncogene. 2000; 19(27):3078-85. DOI: 10.1038/sj.onc.1203642. View

13.

Sun S, Liang X, Zhang X, Liu T, Shi Q, Song Y . Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer. Br J Cancer. 2015; 112(8):1332-9. PMC: 4402453. DOI: 10.1038/bjc.2015.114. View

14.

Thussbas C, Nahrig J, Streit S, Bange J, Kriner M, Kates R . FGFR4 Arg388 allele is associated with resistance to adjuvant therapy in primary breast cancer. J Clin Oncol. 2006; 24(23):3747-55. DOI: 10.1200/JCO.2005.04.8587. View

15.

Hammond M, Hayes D, Dowsett M, Allred D, Hagerty K, Badve S . American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010; 28(16):2784-95. PMC: 2881855. DOI: 10.1200/JCO.2009.25.6529. View

16.

Huang H, Feng H, Qiao H, Ren Z, Zhu G . The prognostic significance of fibroblast growth factor receptor 4 in non-small-cell lung cancer. Onco Targets Ther. 2015; 8:1157-64. PMC: 4447177. DOI: 10.2147/OTT.S81659. View

17.

Xu M, Chen S, Yang W, Cheng X, Ye Y, Mao J . FGFR4 Links Glucose Metabolism and Chemotherapy Resistance in Breast Cancer. Cell Physiol Biochem. 2018; 47(1):151-160. DOI: 10.1159/000489759. View

18.

Tiong K, Tan B, Choo H, Chung F, Hii L, Tan S . Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival. Oncotarget. 2016; 7(36):57633-57650. PMC: 5295378. DOI: 10.18632/oncotarget.9328. View

19.

Coates A, Winer E, Goldhirsch A, Gelber R, Gnant M, Piccart-Gebhart M . Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015. Ann Oncol. 2015; 26(8):1533-46. PMC: 4511219. DOI: 10.1093/annonc/mdv221. View

20.

Cinkaya A, Akin M, Sengul A . Evaluation of treatment outcomes of triple-negative breast cancer. J Cancer Res Ther. 2016; 12(1):150-4. DOI: 10.4103/0973-1482.154000. View