title: Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma.
abstract: OBJECTIVE
  The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes.
  
  
  METHODS
  Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer-specific mortality as the primary outcome.
  
  
  RESULTS
  In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer-specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14-2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer-specific mortality (HR=1.77; 95% CI, 1.18-2.66; P=0.006). Five-year lung cancer-specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer-specific survival (P<0.001 and 0.015, respectively), compared with low mPS.
  
  
  CONCLUSIONS
  This study validates CCP score and mPS as independent prognostic markers for lung cancer-specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Division of Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Eguchi
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Chaft
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: Evans
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kidd
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Kay See
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Dycoco
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Kolquist
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Thaylon
authors.initials: T
authors.lastname: Davis
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hamilton
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Kraig
authors.initials: K
authors.lastname: Yager
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Jones
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.affiliation: Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA.
authors.forename: Anne-Renee
authors.initials: AR
authors.lastname: Hartman
authors.affiliation: Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Adusumilli
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002455:Cell Division / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: CCP score; adjuvant therapy; chemotherapy; molecular prognostic score; overall survival