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Oncol Lett. 2017 Sep;14(3):3817-3824. doi: 10.3892/ol.2017.6621. Epub 2017 Jul 20.

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

Author information

1
Department of Urology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk-do 28644, Republic of Korea.
2
Department of Surgery, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk-do 28644, Republic of Korea.
3
Department of Biomedical Engineering, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Chungcheongbuk-do 28644, Republic of Korea.
4
Department of Urology, School of Medicine, Kyungpook National University Medical Center, Daegu 41404, Republic of Korea.
5
Department of Food and Biotechnology, Chungang University, Seoul 06974, Republic of Korea.
6
Department of Biomaterial Control, Dong-Eui University, Busan 47340, Republic of Korea.

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.

KEYWORDS:

bladder cancer; expression; fibroblast growth factor receptor 3; mutation; prognosis

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