title: ACTN4 copy number increase as a predictive biomarker for chemoradiotherapy of locally advanced pancreatic cancer.
abstract: BACKGROUND
  Several clinical trials have compared chemotherapy alone and chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC) treatment. However, predictive biomarkers for optimal therapy of LAPC remain to be identified.We retrospectively estimated amplification of the ACTN4 gene to determine its usefulness as a predictive biomarker for LAPC.
  
  
  METHODS
  The copy number of ACTN4 in 91 biopsy specimens of LAPC before treatment was evaluated using fluorescence in situ hybridisation (FISH).
  
  
  RESULTS
  There were no statistically significant differences in overall survival (OS) or progression-free survival (PFS) of LAPC between patients treated with chemotherapy alone or with CRT. In a subgroup analysis of patients treated with CRT, patients with a copy number increase (CNI) of ACTN4 had a worse prognosis of OS than those with a normal copy number (NCN) of ACTN4 (P=0.0005, log-rank test). However, OS in the subgroup treated with chemotherapy alone was not significantly different between patients with a CNI and a NCN of ACTN4. In the patients with a NCN of ACTN4, the median survival time of PFS in CRT-treated patients was longer than that of patients treated with chemotherapy alone (P=0.049).
  
  
  CONCLUSIONS
  The copy number of ACTN4 is a predictive biomarker for CRT of LAPC.
authors.affiliation: 1] Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan [2] Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Watabe
authors.affiliation: Division of Molecular Pathology, National Cancer Center Research Institute, Tokyo, 104-0045 Japan.
authors.forename: N
authors.initials: N
authors.lastname: Hiraoka
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Morizane
authors.affiliation: Division of Radiation Oncology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Itami
authors.affiliation: Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo 104-0045, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Okusaka
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Miura
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kakizaki
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kakuya
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kamita
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tsuchida
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Tokyo Medical University, Tokyo 160-0023, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nagakawa
authors.affiliation: Abnova, 9th Floor, No. 108, Jhouzih Street, Neihu District, Taipei City 114, Taiwan.
authors.forename: H
authors.initials: H
authors.lastname: Wilber
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Honda
mesh_terms: D000185:Actinin / Q000235:genetics*; D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor / Q000235:genetics*; D059248:Chemoradiotherapy; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C111453:ACTN4 protein, human; D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D000185:Actinin