title: Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: He
authors.affiliation: Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Division of Gastrointestinal and General Surgery, Department of Surgery Cancer, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Jaw-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Huang
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Ting-Fe
authors.initials: TF
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.affiliation: Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Sung-Wei
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Surgery, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Hao-Hsien
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Radiology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Jui-Lung
authors.initials: JL
authors.lastname: Fang
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Wen-Tsung
authors.initials: WT
authors.lastname: Huang
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan.
authors.forename: Shang-Hung
authors.initials: SH
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000032:analysis / Q000096:biosynthesis*; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: CANCER RESEARCH; COLORECTAL CANCER; RECTAL CANCER