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

Abstract

Fibroblast growth factor receptor 4 (FGFR4) belongs to the receptor tyrosine kinase (RTK) family, and FGFR4 polymorphisms have been implicated in both normal development and cancer, including breast cancer. In the present study, we investigated correlations between polymorphisms in FGFR4 and breast cancer prognosis. The FGFR4 SNPs rs1966265 and rs351855 were genotyped in 747 breast cancer patients using the SNaPshot method. FGFR4 protein expression was detected by immunohistochemistry in 339 samples. SNP rs351855 was correlated with FGFR4 protein expression under dominant and co-dominant models. Lymph node metastasis (LNM), ER (estrogen receptor) status, and molecular subtype were associated with high FGFR4 expression. Univariate analysis revealed rs351855 (CC/CT: P = 0.027, CC/TT: P < 0.001, CC/CT + TT: P = 0.005) to be a prognostic predictor, and multivariate analysis indicated rs351855 (CC/TT: P = 0.005) to be an independent prognostic factor. Kaplan-Meier survival analysis showed that high FGFR4 protein expression was associated with a poor prognosis. SNP rs351855 was correlated with worse outcomes, with a dose-dependent effect. The results of this study show that FGFR4 SNP rs351855 is associated with up-regulation of FGFR4 protein expression and a worse prognosis in breast cancer.

New concept on association of FGFR4 G388R, V10I polymorphisms and risk of cancer

“…Furthermore, stratifying by type of cancer, we observed that this variant is correlated with prostate and breast cancer, but not with lung cancer. Our results are consistent with the studies conducted by Xu et al and Wei et al (Xu et al, 2011;Wei et al, 2018). In subgroup analysis by ethnicity, we also found that FGFR4 R-allele is correlated with an increased risk of cancer in Asian descendants.…”

Fibroblast Growth Factor Receptor 4 as A Prognostic Indicator in Triple-Negative Breast Cancer

“…We also found that high levels of FGFR4 expression had a relationship with LNM in our previous study (Wei, You et al 2018). Consistent with these findings, our data revealed that high FGFR4 expression was correlated with LNM in TNBC patients.…”

“…The impact of FGFR4 on prognosis has been found in different cancers (Li, Zhang et al 2014, Huang, Feng et al 2015, Inokuchi, Murase et al 2017, and we also confirmed that patients with high FGFR4 expression had worse outcomes (Wei, You et al 2018). In the present study, TNBC patients with high FGFR4 expression tended to have shorter survival times than those with low FGFR4 expression ( Figure 2).…”

“…Patient follow-up was conducted as our previous study (Wei, You et al 2018). It was conducted on a scheduled basis until patient death or the end of the observation period (May 1st, 2016).…”

“…FGFR4 IHC was performed using a rabbit anti-FGFR4 monoclonal antibody (1:200 dilution, Abcam: ab41948) as previously described (Wei, You et al 2018). IHC for ER, PR, HER2, Ki67 and p53 (ZSBG-BIO: ZM-0104, ZM-0215, ZM-0065, ZM-0165, ZM-0405) was performed similarly.…”