title: Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: correlative study in Japan Clinical Oncology Group Trial JCOG9912.
abstract: BACKGROUND
  Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer.
  
  
  METHODS
  Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point.
  
  
  RESULTS
  Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08-1.75; P = 0.010], performance status ≥ 1 (HR 1.45; 95% CI 1.13-1.86; P = 0.004), and number of metastatic sites ≥ 2 (HR 1.66; 95% CI 1.28-1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1.
  
  
  CONCLUSIONS
  These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.
  
  
  BACKGROUND
  C000000062, www.umin.ac.jp.
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo. Electronic address: yayamada@ncc.go.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki.
authors.forename: N
authors.initials: N
authors.lastname: Boku
authors.affiliation: Department of Gastrointestinal Medical Oncology, Shikoku Cancer Center, Matsuyama.
authors.forename: T
authors.initials: T
authors.lastname: Nishina
authors.affiliation: Department of Gastroenterology, Saitama Cancer Center, Kita-adachi.
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Gastroenterology, Chiba Cancer Center, Chiba.
authors.forename: T
authors.initials: T
authors.lastname: Denda
authors.affiliation: Department of Clinical Oncology, Kobe City Medical Center General Hospital, Kobe.
authors.forename: A
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology, Keio University, School of Medicine, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Hamamoto
authors.affiliation: Department of Gastroenterology, Showa University, School of Medicine, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Konishi
authors.affiliation: Department of Clinical Oncology, Tonan Hospital, Sapporo.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuji
authors.affiliation: Department of Gastroenterology, Ibaraki Prefectural Central Hospital, Kasama.
authors.forename: K
authors.initials: K
authors.lastname: Amagai
authors.affiliation: Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama.
authors.forename: S
authors.initials: S
authors.lastname: Ohkawa
authors.affiliation: Department of Gastroenterology, Yokohama Municipal Citizen's Hospital, Yokohama.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Gastroenterological Oncology, Hyogo Cancer Center, Akashi.
authors.forename: H
authors.initials: H
authors.lastname: Nishisaki
authors.affiliation: Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya.
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.affiliation: Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: A
authors.initials: A
authors.lastname: Takashima
authors.affiliation: JCOG Data Center/Operations Office, National Cancer Center, Tokyo.
authors.forename: J
authors.initials: J
authors.lastname: Mizusawa
authors.affiliation: JCOG Data Center/Operations Office, National Cancer Center, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: National Cancer Center, Exploratory Oncology Research and Clinical Trial Center, Kashiwa, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D004338:Drug Combinations; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D000077146:Irinotecan; D008297:Male; D010094:Oxonic Acid / Q000627:therapeutic use; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D013534:Survival; D005641:Tegafur / Q000627:therapeutic use; D013940:Thymidylate Synthase / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000077146:Irinotecan; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin
keywords: dihydropyrimidine dehydrogenase; excision repair cross-complementing gene 1; gastric cancer; prognostic factor; thymidylate synthase; vascular endothelial growth factor