Prognostic significance of fibroblast growth factor receptor 4 polymorphisms on biochemical recurrence after radical prostatectomy in a Chinese population

Abstract

Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane receptor with ligand-induced tyrosine kinase activity and is involved in various biological and pathological processes. Several polymorphisms of FGFR4 are associated with the incidence and mortality of numerous cancers, including prostate cancer. In this study, we investigated whether the polymorphisms of FGFR4 influence the biochemical recurrence of prostate cancer in Chinese men after radical prostatectomy. Three common polymorphisms (rs1966265, rs2011077, and rs351855) of FGFR4 were genotyped from 346 patients with prostate cancer by using the Sequenom MassARRAY system. Kaplan–Meier curves and Cox proportional hazard models were used for survival analysis. Results showed biochemical recurrence (BCR) free survival was significantly affected by the genotypes of rs351855 but not influenced by rs1966265 and rs2011077. After adjusting for other variables in multivariable analysis, patients with rs351855 AA/AG genotypes showed significantly worse BCR-free survival than those with the GG genotype (HR = 1.873; 95% CI, 1.209–2.901; P = 0.005). Hence, FGFR4 rs351855 could be a novel independent prognostic factor of BCR after radical prostatectomy in the Chinese population. This functional polymorphism may also provide a basis for surveillance programs. Additional large-scale studies must be performed to validate the significance of this polymorphism in prostate cancer.

Prognostic implications of fibroblast growth factor receptor 4 polymorphisms in primary breast cancer

“…The FGFR4 SNP rs351855, corresponding to the Gly388Arg substitution, is an important polymorphism that is biologically functional and can affect the transmembrane domain of the protein . FGFR4 is overexpressed in many cancers, including gastric cancer, non‐small cell lung cancer, colorectal cancer, and breast cancer .…”

“…SNP rs351855 (CC/TT) was an independent prognostic indicator in our multivariate analysis (Table ), and Kaplan‐Meier analysis revealed that the survival rate of patients was decreased along with an increase in MAF (Figure ), in accordance with previous studies. In addition, Chen et al proved that biochemical recurrence‐free survival time decreases along with an increase in A allele frequency in prostate cancer. Spinola et al found that lung adenocarcinoma patients carrying the Arg allele (Arg/Arg or Gly/Arg) had a significantly higher occurrence of death compared to those carrying the Gly allele, and non‐Hodgkin lymphoma G allele carriers had a significantly longer survival time .…”

“…and Kaplan-Meier analysis revealed that the survival rate of patients was decreased along with an increase in MAF (Figure 2), in accordance with previous studies. In addition, Chen et al 24 33 These findings suggest that FGFR4 polymorphisms might have important effects on breast cancer. A molecular mechanism underlying the genetic association of rs351855 with accelerated cancer progression has been reported by Ulaganathan et al 34 The authors proposed that transmembrane-spanning segments of FGFR4 can be altered by substitution of conserved Gly388 with a charged Arg, exposing a binding site for membrane-proximal cytoplasmic signal transducer and activator of transcription 3 (STAT3), thereby enhancing STAT3 tyrosine phosphorylation by recruiting the proteins to the inner cellular membrane.…”

Functional FGFR4 Gly388Arg polymorphism contributes to oral squamous cell carcinoma susceptibility

“…Heinzle et al [ 20 ] demonstrated that among patients with colorectal cancer, FGFR4 A allele carriers had a five-fold higher risk of tumors that were stage II or higher. Chen et al [ 21 ] reported that patients with the FGFR4 SNP rs351855 AA or AG genotype exhibited a poorer biochemical recurrence-free survival than did those with the GG genotype. Therefore, the SNP rs351855 of FGFR4 polymorphism might provide a basis for surveillance programs.…”

FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis

“…In addition, the FGFR4 Arg388 allele has been linked to advanced stage and more frequent lymph node (LN) metastases than the wild-type homozygote (Gly/Gly) in the cohorts of CRC ( 12 ), BC ( 12 , 34 ), PC ( 15 ), and LC ( 18 ). It has also been implicated in reducing disease-free survival or overall survival in patients with BC ( 12 , 35 ), HNSCC ( 24 , 25 , 36 ), GC ( 37 , 38 ), PC ( 39 ), CRC ( 40 ), and LC ( 9 , 41 ). Interestingly, Serra et al.…”