title: Klotho predicts good clinical outcome in patients with limited-disease small cell lung cancer who received surgery.
abstract: BACKGROUND
  The important role of surgery in early-stage small cell lung cancer (SCLC) has been recognized, and curative surgical resection is recommended. However, the role of adjuvant chemotherapy for stage I SCLC has not yet been evaluated, and novel approaches focusing on the specific genomic characteristics of SCLC may be invaluable for customized therapy. In this study, we focused on the Klotho gene, which is an anti-aging gene known to be a potential tumor suppressor. We investigated whether the expression of Klotho, assessed by immunohistochemistry, can predict survival in patients with resected SCLC.
  
  
  METHODS
  The medical records of patients diagnosed as having limited-disease (LD) SCLC and treated by surgical resection (n=30) at Tokyo Medical University Hospital were retrospectively reviewed. The expression status of Klotho, and of the ATP-binding cassette (ABC) transporters MRP1, MDR and breast cancer resistant protein (BCRP), which can cause resistance to anticancer drugs, including irinotecan, was assessed by immunohistochemical analysis in resected surgical specimens of patients with early-stage SCLC.
  
  
  RESULTS
  Of the 30 patients, Klotho expression was seen in the specimens from 18 patients (60.0%), but not in those of the remaining 12 patients (40.0%). The immunostaining for Klotho was mostly localized in the cytoplasm. The expression of Klotho was significantly associated with the overall survival (OS) (ratio 0.088; 95% confidence interval 0.019-0.409; P=0.002). The administration of perioperative chemotherapy had no significant effect in improving the survival, as assessed by the Kaplan-Meier method. However, the patients showing Klotho expression in the resected specimens in p-stage I and II, may have benefited from perioperative chemotherapy. A multivariate analysis revealed no significant association between the expression status of MRP1, MDR or BCRP and the OS.
  
  
  CONCLUSIONS
  Expression of Klotho was predictive of a favorable outcome following resection in limited-disease SCLC patients, and the Klotho expression status may serve as a new biomarker for the need of additional therapies to be developed in the future.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery 1, Tokyo Medical University, 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. jusuda@tokyo-med.ac.jp
authors.forename: Jitsuo
authors.initials: J
authors.lastname: Usuda
authors.forename: Shuji
authors.initials: S
authors.lastname: Ichinose
authors.forename: Taichirou
authors.initials: T
authors.lastname: Ishizumi
authors.forename: Keishi
authors.initials: K
authors.lastname: Ohtani
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Inoue
authors.forename: Hisashi
authors.initials: H
authors.lastname: Saji
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kakihana
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Osamu
authors.initials: O
authors.lastname: Uchida
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nomura
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohira
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ikeda
mesh_terms: D000368:Aged; D017024:Chemotherapy, Adjuvant; D055088:Early Detection of Cancer; D005260:Female; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D000090265:Klotho Proteins; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011013:Pneumonectomy; D011237:Predictive Value of Tests; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000601:surgery
chemical_list: D005966:Glucuronidase; D000090265:Klotho Proteins