Expression levels of FGFR3 as a prognostic marker for the progression of primary pT1 bladder cancer and its association with mutation status

Kang,Ho Won; Kim,Ye‑Hwan; Jeong,Pildu; Park,Cheol; Kim,Won Tae; Ryu,Dong Hee; Cha,Eun‑Jong; Ha,Yun‑Sok; Kim,Tae‑Hwan; Kwon,Tae Gyun; Moon,Sung‑Kwon; Choi,Yung Hyun; Yun,Seok‑Joong; Kim,Wun‑Jae

doi:10.3892/ol.2017.6621

Expression levels of FGFR3 as a prognostic marker for the progression of primary pT1 bladder cancer and its association with mutation status

Authors:
- Ho Won Kang
- Ye‑Hwan Kim
- Pildu Jeong
- Cheol Park
- Won Tae Kim
- Dong Hee Ryu
- Eun‑Jong Cha
- Yun‑Sok Ha
- Tae‑Hwan Kim
- Tae Gyun Kwon
- Sung‑Kwon Moon
- Yung Hyun Choi
- Seok‑Joong Yun
- Wun‑Jae Kim
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Affiliations: Department of Urology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea, Department of Surgery, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea, Department of Biomedical Engineering, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk‑do 28644, Republic of Korea, Department of Urology, School of Medicine, Kyungpook National University Medical Center, Daegu 41404, Republic of Korea, Department of Food and Biotechnology, Chungang University, Seoul 06974, Republic of Korea, Department of Biomaterial Control, Dong‑Eui University, Busan 47340, Republic of Korea
Published online on: July 20, 2017 https://doi.org/10.3892/ol.2017.6621
Pages: 3817-3824

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Abstract

The present study examined the utility of fibroblast growth factor receptor 3 (FGFR3) mutation status and gene expression as a prognostic marker in primary pT1 bladder cancer (BC). A total of 120 patients with primary pT1 BC were enrolled. FGFR3 mutation status was determined by direct sequencing and FGFR3 mRNA expression level was determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis. The results were compared with the clinicopathological parameters, and the prognostic value of FGFR3 was evaluated by Kaplan‑Meier analysis and a multivariate Cox regression test. FGFR3 mutations were identified in 48/120 (40.0%) patients with pT1 BC. FGFR3 mRNA expression level was significantly higher in those with BC harboring FGFR3 mutations (P<0.001). Low FGFR3 expression level was associated with high‑grade tumors and cancer progression (P=0.006 and P=0.001), whereas FGFR3 mutation status was not associated with cancer progression. Kaplan‑Meier analysis revealed a similar result (log‑rank, P<0.001). Multivariate analysis identified low FGFR3 expression level (odds ratio, 3.300; 95% confidence interval, 1.310‑8.313; P=0.011) as an independent predictor of cancer progression. Stratification by exon site of FGFR3 mutations yielded significant differences in mRNA expression level. None of the patients with BC harboring FGFR3 mutations in exon 9 demonstrated disease progression. The mRNA expression level of the FGFR3 gene may be used to precisely identify subsets of patients with pT1 BC that have a relatively better prognosis. The prognostic influences of FGFR3 mutations may be modulated by the exon site of FGFR3 mutations.

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