title: Integrating differential pathway analysis with Monte Carlo cross-validation reveals seed cross-talks in non-small cell lung carcinoma.
abstract: OBJECTIVE
  The objective of this study was to identify seed pathway cross-talks in non-small cell lung carcinoma (NSCLC), and to reveal potential pathological mechanism at molecular level systematically.
  
  
  METHODS
  Differentially expressed genes (DEGs) between NSCLC and normal controls were identified using quantile- adjusted conditional maximum likelihood (QCML) method. Subsequently, differential pathways (DPs) enriched by DEGs were determined according to the Ingenuity Pathways Analysis )IPA) pathways and Fisher's exact test. A discriminating score )DS) was computed for each pair of DPs also called as cross-talk, and random forest )RF) algorithm was implemented to investigated hub cross-talks. Finally, global cross-talks with repeated times > 5 were calculated by Monte Carlo Cross-Validation )MCCV). By taking intersections between hub cross-talks and global crosstalks, we obtained seed cross-talks.
  
  
  RESULTS
  We obtained 122 DEGs and 5 DPs between NSCLC samples and normal controls. Based on DS and RF algorithm, 5 hub cross-talks with best area under the curve )AUC) were identified, of which Agranulocyte Adhesion and Diapedesis, and IL-17A Signaling in Fibroblasts were the best with AUC=0.996. After intersected with global cross-talks, we gained 2 seed cross-talks (Agranulocyte Adhesion and Diapedesis, Granulocyte Adhesion and Diapedesis and Agranulocyte Adhesion and Diapedesis, Glutathione Redox Reactions I).
  
  
  CONCLUSIONS
  Two seed cross-talks were identified and validated by MCCV, which may give insights for revealing pathological mechanism and potential biomarkers for target therapy in NSCLC.
authors.affiliation: Department of Chest Surgery, the 309th Hospital, PLA, Beijing, 100091, China.
authors.forename: Meng-Li
authors.initials: ML
authors.lastname: Zheng
authors.forename: Nai-Kang
authors.initials: NK
authors.lastname: Zhou
authors.forename: Cheng-Hua
authors.initials: CH
authors.lastname: Luo
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D016013:Likelihood Functions; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009010:Monte Carlo Method; D020411:Oligonucleotide Array Sequence Analysis; D060066:Protein Interaction Maps; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor