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Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy
  1. Chien-Feng Li1,2,3,4,
  2. Hong-Lin He5,
  3. Jaw-Yuan Wang4,6,
  4. Hsuan-Ying Huang7,
  5. Ting-Fe Wu3,
  6. Chung-Hsi Hsing8,
  7. Sung-Wei Lee9,
  8. Hao-Hsien Lee10,
  9. Jui-Lung Fang11,
  10. Wen-Tsung Huang12,
  11. Shang-Hung Chen2,12
  1. 1Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
  2. 2National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
  3. 3Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan
  4. 4Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  5. 5Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
  6. 6Division of Gastrointestinal and General Surgery, Department of Surgery Cancer, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
  7. 7Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
  8. 8Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan
  9. 9Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
  10. 10Department of Surgery, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
  11. 11Department of Radiology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
  12. 12Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
  1. Correspondence to Dr Shang Hung Chen, Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, No.201, Taikang, Taikang Vil., Liuying Dist., Tainan City 736, Taiwan; bryanchen0615{at}gmail.com

Abstract

Aims Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of the fibroblast growth factor/fibroblast growth factor receptor (FGFR) signalling pathway has been recognised; however, its clinical significance in rectal cancer has not been elucidated. In this study, we identify and validate targetable drivers associated with the FGFR signalling pathway in rectal cancer patients treated with CCRT.

Methods Using a published transcriptome of rectal cancers, we found FGFR2 gene significantly predicted response to CCRT. The expression levels of FGFR2, using immunohistochemistry assays, were further evaluated in 172 rectal cancer specimens that had not received any treatment. Expression levels of FGFR2 were statistically correlated with major clinicopathological features and clinical survival in this valid cohort.

Results High expression of FGFR2 was significantly related to advanced pretreatment tumour (p=0.022) and nodal status (p=0.026), post-treatment tumour (p<0.001) and nodal status (p=0.004), and inferior tumour regression grade (p<0.001). In survival analyses, high expression of FGFR2 was significantly associated with shorter local recurrence-free survival (p=0.0001), metastasis-free survival (MeFS; p=0.0003) and disease-specific survival (DSS; p<0.0001). Notably, high expression of FGFR2 was independently predictive of worse outcomes for MeFS (p=0.002, HR=5.387) and DSS (p=0.004, HR=4.997).

Conclusions High expression of FGFR2 is correlated with advanced tumour stage, poor therapeutic response and worse survival in rectal cancer patients receiving neoadjuvant CCRT. These findings indicate that FGFR2 is a prognostic factor for treating rectal cancer.

  • COLORECTAL CANCER
  • RECTAL CANCER
  • CANCER RESEARCH

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