title: Resection of non-small cell lung cancers reverses tumor-induced gene expression changes in the peripheral immune system.
abstract: OBJECTIVE
  To characterize the interactions of non-small cell lung cancer (NSCLC) tumors with the immune system at the level of mRNA and microRNA (miRNA) expression and to define expression signatures that characterize the presence of a malignant tumor versus a nonmalignant nodule.
  
  
  METHODS
  We have examined the changes of both mRNA and miRNA expression levels in peripheral blood mononuclear cells (PBMC) between paired samples collected from NSCLC patients before and after tumor removal using Illumina gene expression arrays.
  
  
  RESULTS
  We found that malignant tumor removal significantly changes expression of more than 3,000 protein-coding genes, especially genes in pathways associated with suppression of the innate immune response, including natural killer cell signaling and apoptosis-associated ceramide signaling. Binding sites for the ETS domain transcription factors ELK1, ELK4, and SPI1 were enriched in promoter regions of genes upregulated in the presence of a tumor. Additional important regulators included five miRNAs expressed at significantly higher levels before tumor removal. Repressed protein-coding targets of those miRNAs included many transcription factors, several involved in immunologically important pathways. Although there was a significant overlap in the effects of malignant tumors and benign lung nodules on PBMC gene expression, we identified one gene panel which indicates a tumor or nodule presence and a second panel that can distinguish malignant from nonmalignant nodules.
  
  
  CONCLUSIONS
  A tumor presence in the lung influences mRNA and miRNA expression in PBMC and this influence is reversed by tumor removal. These results suggest that PBMC gene expression signatures could be used for lung cancer diagnosis.
authors.affiliation: The Wistar Institute, Philadelphia, Pennsylvania, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Kossenkov
authors.forename: Anil
authors.initials: A
authors.lastname: Vachani
authors.forename: Celia
authors.initials: C
authors.lastname: Chang
authors.forename: Calen
authors.initials: C
authors.lastname: Nichols
authors.forename: Shere
authors.initials: S
authors.lastname: Billouin
authors.forename: Wenhwai
authors.initials: W
authors.lastname: Horng
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.forename: Michael K
authors.initials: MK
authors.lastname: Showe
authors.forename: Louise C
authors.initials: LC
authors.lastname: Showe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000601:surgery; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014157:Transcription Factors