title: REG Iα is a biomarker for predicting response to chemotherapy with S-1 plus cisplatin in patients with unresectable stage IV gastric cancer.
abstract: BACKGROUND
  The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC.
  
  
  METHODS
  A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry.
  
  
  RESULTS
  Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells.
  
  
  CONCLUSIONS
  In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.
authors: Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
authors: A
authors: A
authors: Sekikawa
authors: H
authors: H
authors: Fukui
authors: X
authors: X
authors: Zhang
authors: T
authors: T
authors: Maruo
authors: T
authors: T
authors: Tsumura
authors: Y
authors: Y
authors: Okabe
authors: T
authors: T
authors: Wakasa
authors: Y
authors: Y
authors: Osaki
authors: T
authors: T
authors: Chiba
authors: T
authors: T
authors: Tomita
authors: T
authors: T
authors: Oshima
authors: J
authors: J
authors: Watari
authors: H
authors: H
authors: Miwa
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000627:therapeutic use*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D051847:Lithostathine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D004338:Drug Combinations; D051847:Lithostathine; C497617:REG1A protein, human; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D005472:Fluorouracil