- Gastrointestinal cancer
-
FGFR4 Gly388Arg Polymorphism Affects the Progression of Gastric Cancer by Activating STAT3 Pathway to Induce Epithelial to Mesenchymal Transition
-
Yanwei Ye, Jie Li, Dongbao Jiang, Jingjing Li, Chuangfeng Xiao, Yingze Li, Chao Han, Chunlin Zhao
-
Cancer Res Treat. 2020;52(4):1162-1177. Published online May 25, 2020
-
DOI: https://doi.org/10.4143/crt.2020.138
-
-
 Abstract
 PDF PubReader ePub
- Purpose
Fibroblast growth factor receptor 4 (FGFR4) plays a critical role in cancer progression involving in tumor proliferation, invasion, and metastasis. This study clarified the role of FGFR4-Arg388 variant in gastric cancer (GC), and more importantly highlighted the possibility of this single nucleotide polymorphism (SNP) as potential therapeutic targets.
Materials and Methods
FGFR4 polymorphism was characterized in advanced GC patients to perform statistical analysis. FGFR4-dependent signal pathways involving cell proliferation, invasion, migration, and resistance to oxaliplatin (OXA) in accordance with the SNP were also assessed in transfected GC cell lines.
Results
Among 102 GC patients, the FGFR4-Arg388 patients showed significantly higher tumor stage (p=0.047) and worse overall survival (p=0.033) than the Gly388 patients. Immunohistochemical results showed that FGFR4-Arg388 patients were more likely to have higher vimentin (p=0.025) and p-STAT3 (p=0.009) expression compared with FGFR4-Gly388 patients. In transfected GC cells, the overexpression of FGFR4-Arg388 variant increased proliferation and invasion of GC cells, increasing resistance of GC cells to OXA compared with cells overexpressing the Gly388 allele.
Conclusion
The exploration mechanism may be through FGFR4-Arg388/STAT3/epithelial to mesenchymal transition axis regulating pivotal oncogenic properties of GC cells. The FGFR4-Arg388 variant may be a biomarker and a candidate target for adjuvant treatment of GC.
-
Citations
Citations to this article as recorded by  - Schlafen 11 predicts response to platinum-based chemotherapy in gastric cancers
Tsuyoshi Takashima, Daiki Taniyama, Naoya Sakamoto, Maika Yasumoto, Ryuichi Asai, Takuya Hattori, Ririno Honma, Pham Quoc Thang, Shoichi Ukai, Ryota Maruyama, Kenji Harada, Kazuya Kuraoka, Kazuaki Tanabe, Atsuo T. Sasaki, Hideki Ohdan, Eiichi Morii, Junko
British Journal of Cancer.2021; 125(1): 65. CrossRef - FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis
Jung Han Kim, Soo Young Jeong, Hyun Joo Jang, Sung Taek Park, Hyeong Su Kim
Frontiers in Oncology.2021;[Epub] CrossRef - FGF/FGFR-Dependent Molecular Mechanisms Underlying Anti-Cancer Drug Resistance
Jakub Szymczyk, Katarzyna Sluzalska, Izabela Materla, Lukasz Opalinski, Jacek Otlewski, Malgorzata Zakrzewska
Cancers.2021; 13(22): 5796. CrossRef
-
6,403
View
-
152
Download
-
5
Web of Science
-
3
Crossref
|
KCA
