title: A 25-signal proteomic signature and outcome for patients with resected non-small-cell lung cancer.
abstract: BACKGROUND
  Among patients with non-small-cell lung cancer (NSCLC), those with poor prognosis cannot be distinguished from those with good prognosis.
  
  
  METHODS
  Matrix-assisted laser desorption-ionization mass spectrometry was used to analyze protein profiles of 174 specimens from NSCLC tumors and 27 specimens from normal lung tissue and to derive a prognosis-associated proteomic signature. Frozen resected tissue specimens were randomly divided into a training set (116 NSCLC and 20 normal lung specimens) and an independent, blinded validation set (58 NSCLC and seven normal lung specimens). Mass spectrometry signals from training set specimens that were differentially associated with specimens from patients with a high risk of recurrence (i.e., who died within 5 years of surgical treatment because of relapse) compared with those from patients with a low risk of recurrence (i.e., alive with no symptoms of relapse after a median follow-up of 89 months) were selected by use of the Fisher's exact test, the Kruskal-Wallis test, and the significance analysis of microarray test. These signals were used to build an individualized, weighted voting-based prognostic signature. The signature was then validated in the independent dataset. Survival was assessed by multivariable Cox regression analysis. Proteins corresponding to individual signals were identified by ion-trap mass spectrometry coupled with high-performance liquid chromatography. All statistical tests were two-sided.
  
  
  RESULTS
  From 2630 mass spectrometry signals from specimens in the training cohort, we derived a signature of 25 signals that was associated with both relapse-free survival and overall survival. Among stage I NSCLC patients in the validation set, the signature was statistically significantly associated with both overall survival (hazard ratio [HR] of death for patients in the high-risk group compared with those in the low-risk group = 61.1, 95% confidence interval [CI] = 8.9 to 419.2, P<.001) and relapse-free survival (HR of relapse = 11.7, 95% CI = 3.1 to 44.8, P<.001). Proteins corresponding to signals in the signature were identified that had various cellular functions, including ribosomal protein L26-like 1, acylphosphatase, and phosphoprotein enriched in astrocytes 15.
  
  
  CONCLUSIONS
  We defined a mass spectrometry signature that was associated with survival among NSCLC patients and appeared to distinguish those with poor prognosis from those with good prognosis.
authors.affiliation: Institute for Advanced Research, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan. kyana@med.nagoya-u.ac.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomida
authors.forename: Yukako
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009363:Neoplasm Proteins