title: Association of PDCD1 and CTLA-4 Gene Expression with Clinicopathological Factors and Survival in Non-Small-Cell Lung Cancer: Results from a Large and Pooled Microarray Database.
abstract: BACKGROUND
  Immune checkpoint blockade is being investigated in clinical trials and showed great potential in lung cancer. The prognostic roles of and clinicopathological factors associated with immune checkpoint gene expression, CTLA-4 and PDCD1 remain largely undefined, which encodes cytotoxic-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1), respectively.
  
  
  METHODS
  We used a lung cancer database of 1715 patients measured by Affymetrix microarrays to analyze the association of gene expression with clinicopathological factors and survival. Hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) were calculated. Cutoffs were determined by median across the entire database.
  
  
  RESULTS
  In 909 patients with histology information, significantly higher PDCD1 and CTLA-4 expression were found in squamous carcinoma than adenocarcinoma. In 848 patients with known smoking history, current/former smokers were found to have significantly elevated gene expression compared with nonsmokers. Significant higher expression of both genes were found in TNM stage II versus I. Higher expression of PDCD1 predicted worse OS in univariate analysis, but not in multivariate (HR: 1.22; 95% CI: 0.53-2.79). CTLA-4 was marginally significant in univariate analysis of the entire set (HR: 1.15; 95% CI: 0.99-1.34). In patients with information for multivariate analysis, higher expression of CTLA-4 was associated with worse OS (HR: 1.96; 95% CI: 1.18-3.31).
  
  
  CONCLUSIONS
  In this study with large number of patients, PDCD1 and CTLA-4 expression is significantly higher in squamous carcinoma and current/former smokers. Higher expression of CTLA-4, but not PDCD1 predicts worse survival.
authors.affiliation: *Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, †Huaxi Student Society of Oncology Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China; ‡MTA TTK Lendület Cancer Biomarker Research Group, §2nd Department of Pediatrics, Semmelweis University, and ‖MTA-SE Pediatrics and Nephrology Research Group, Budapest, Hungary.
authors.forename: Lei
authors.initials: L
authors.lastname: Deng
authors.forename: Balazs
authors.initials: B
authors.lastname: Gyorffy
authors.forename: Feifei
authors.initials: F
authors.lastname: Na
authors.forename: Baoqing
authors.initials: B
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Lan
authors.forename: Jianxin
authors.initials: J
authors.lastname: Xue
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: You
authors.initials: Y
authors.lastname: Lu
mesh_terms: D060908:CTLA-4 Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor