title: Effect evaluation of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer patients using microarray data.
abstract: OBJECTIVE
  This study was performed to evaluate the therapeutic effect of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Dataset GSE39345 from patients who underwent cisplatin-gemcitabine combination chemotherapy and normal controls was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using Limma package and divided into 3 datasets: unique DEGs in NSCLC before chemotherapy vs. control samples (dataset A), common DEGs (dataset B), unique DEGs in NSCLC after chemotherapy vs. control samples (dataset C). Enrichment analysis was to identify functions or pathways of DEGs. Protein-protein interaction (PPI) analysis was to identify hub nodes and interacting pairs in dataset C and constructed into PPI network using Cytoscape software, followed by screening of small molecules using Connectivity Map.
  
  
  RESULTS
  Herein, 230 unique DEGs in dataset A, 584 common DEGs in dataset B and 1562 unique DEGs in dataset C were obtained. The 230 DEGs were significantly enriched in methylation and positive regulation of cell differentiation; the 584 DEGs were significantly enriched in positive regulation of cell differentiation and cytokine-cytokine receptor interaction pathway; the 1562 DEGs were enriched in functions associated with defense response. RELA and PLCB3 correlated with PLCE1 and INADL were hub nodes in the PPI network. Cefoperazone was the small molecule negatively correlated with DEGs.
  
  
  CONCLUSIONS
  Chemotherapy could prevent genes from aberrant methylation, partially restore cell differentiation process, fail to regulate cytokine-cytokine receptor interaction and induce weakened defense response. Cefoperazone could be used as a supplementary drug.
authors.affiliation: Department of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. danwangdr@163.com.
authors.forename: G F
authors.initials: GF
authors.lastname: Ma
authors.forename: R F
authors.initials: RF
authors.lastname: Zhang
authors.forename: K J
authors.initials: KJ
authors.lastname: Ying
authors.forename: D
authors.initials: D
authors.lastname: Wang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D046228:Microarray Analysis; D020360:Neoadjuvant Therapy; D000093542:Gemcitabine
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine