title: Three immunomarker support vector machines-based prognostic classifiers for stage IB non-small-cell lung cancer.
abstract: OBJECTIVE
  Approximately 30% of patients with stage IB non-small-cell lung cancer (NSCLC) die within 5 years after surgery. Current staging methods are inadequate for predicting the prognosis of this particular subgroup. This study identifies prognostic markers for NSCLC.
  
  
  METHODS
  We used computer-generated random numbers to study 148 paraffin-embedded specimens for immunohistochemical analysis. We studied gene expression in paraffin-embedded specimens of lung cancer tissue from 73 randomly selected patients with stage IB NSCLC who had undergone radical surgical resection and evaluated the association between the level of expression and survival. We used support vector machines (SVM)-based methods to develop three immunomarker-SVM-based prognostic classifiers for stage IB NSCLC. For validation, we used randomly assigned specimens from 75 other patients.
  
  
  RESULTS
  We devised three immunomarker-SVM-based prognostic classifiers, including SVM1, SVM2, and SVM3, to refine prognosis of stage IB NSCLC successfully. The SVM1 model integrates age, cancer cell type, and five markers, including CD34MVD, EMA, p21ras, p21WAF1, and tissue inhibitors of metalloproteinases (TIMP) -2. The SVM2 model integrates age, cancer cell type, and 19 markers, including BCL2, caspase-9, CD34MVD, low-molecular-weight cytokeratin, high-molecular-weight cytokeratin, cyclo-oxygenase-2, EMA, HER2, matrix metalloproteinases (MMP) -2, MMP-9, p16, p21ras, p21WAF1, p27kip1, p53, TIMP-1, TIMP-2, vascular endothelial growth factor (VEGF), and beta-catenin. The SVM3 model consists of SVM1 and SVM2. The three models were independent predictors of overall survival. We validated the classifiers with data from an independent cohort of 75 patients with stage IB NSCLC.
  
  
  CONCLUSIONS
  The three immunomarker-SVM-based prognostic characteristics are closely associated with overall survival among patients with stage IB NSCLC.
authors.affiliation: Department of Thoracic Oncology, Cancer Center of Sun Yat-Sen University, 651 Dongfeng Rd E, Guangzhou 510060, People's Republic of China, USA.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Zhu
authors.forename: Bing-Yu
authors.initials: BY
authors.lastname: Sun
authors.forename: Yun
authors.initials: Y
authors.lastname: Ma
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Hao
authors.initials: H
authors.lastname: Long
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Fu
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Su
authors.forename: Qiu-Liang
authors.initials: QL
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Ling
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Ze-Ming
authors.initials: ZM
authors.lastname: Xie
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.forename: Tie-Hua
authors.initials: TH
authors.lastname: Rong
mesh_terms: D000328:Adult; D000368:Aged; D001185:Artificial Intelligence; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D003936:Diagnosis, Computer-Assisted; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor