title: MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients.
abstract: OBJECTIVE
  Methylthioadenosine phosphorylase (MTAP), a ubiquitously expressed protein, plays important roles in purine biosynthesis. Locating near to each other on chromosome 9p21-22, codeletion of the MTAP and p16(Ink4A) genes have been reported in non-small cell lung cancer (NSCLC). The aim of this study is to determine the respective prognostic value of MTAP and p16 by considering their correlation in NSCLC patients.
  
  
  METHODS
  We analyzed MTAP and p16 protein expression by immunohistochemical staining on 99 NSCLC tissue microarray samples. The association between MTAP and p16 expression levels and prognosis were analyzed using the Kaplan-Meier method and Cox proportional hazards model for prognosis.
  
  
  RESULTS
  Patients with a low MTAP expression level had poor overall survival (P = 0.010) and disease-free survival (P = 0.002). Low p16 expression indicated a trend toward poor overall survival (P = 0.138) and disease-free survival (P = 0.199). There was a significant positive correlation between MTAP and p16 expression levels (Spearman's ρ = 0.402, P < 0.001). By multivariate analyses, the MTAP expression level retained its independent prognostic power and p16 expression loss of the correlation with prognosis. Concordant loss of MTAP and p16 expression was observed in 24 out of 99 patients (24.2%). Patients with concordant loss of MTAP and p16 expression had the worst prognosis compared to patients with high expression of both markers.
  
  
  CONCLUSIONS
  MTAP expression is an independent prognostic factor and has greater prognostic significance than p16 expression in NSCLC. Concordant loss of MTAP and p16 expression indicates poor outcomes in lung cancer patients.
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: C-Y
authors: CY
authors: Su
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Y-C
authors: YC
authors: Chang
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: Y-C
authors: YC
authors: Chan
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors: T-C
authors: TC
authors: Lin
authors: Deapartment of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
authors: M-S
authors: MS
authors: Huang
authors: Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan. Electronic address: chjeya@cc.kmu.edu.tw.
authors: C-J
authors: CJ
authors: Yang
authors: Genomics Research Center, Academia Sinica, Taipei, Taiwan. Electronic address: mhsiao@gate.sinica.edu.tw.
authors: M
authors: M
authors: Hsiao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000378:metabolism* / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase
keywords: Immunohistochemistry; Lung cancer; Methylthioadenosine phosphorylase (MTAP); Prognosis; p16