title: Main histologic types of non-small-cell lung cancer differ in expression of prognosis-related genes.
abstract: BACKGROUND
  There is increasing evidence that suggests that particular histopathologic types of non-small-cell lung cancer (NSCLC) display distinct molecular characteristics. We analyzed, in lung squamous cell carcinoma (SCC) and adenocarcinoma (AC), the expression of 8 genes that constitute 2 previously reported prognostic expression signatures in NSCLC.
  
  
  METHODS
  Fresh-frozen tumor and normal lung samples were obtained at surgery from 135 patients with stage I-III NSCLC (89 (65.9%) SCC, 46 (34.1%) AC). Expression of CSF1 (colony stimulating factor for macrophages), carbonic anhydrase 9 (CA9), epithelial growth factor receptor (EGFR), dual specificity phosphatase 6 (DUSP6), v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), monocyte to macrophage differentiation-associated (MMD), lymphocyte-specific protein tyrosine kinase (LCK) and signal transducer and activator of transcription 1 (STAT1) was assessed in SCC, AC, and in normal lung by quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR). Metastasis-free survival was analyzed according to the median value of gene expression in the entire NSCLC cohort and separately in SCC and AC.
  
  
  RESULTS
  Expression of CA9, CSF1, DUSP6, STAT1, and MMD differed between NSCLC and normal lung. EGFR was more abundant in SCC compared with AC, whereas the reverse was true for DUSP6 and ERBB3. A high expression of CSF1 correlated with shorter metastasis-free survival in the entire NSCLC group (P = .016) and in SCC (P = .049) and AC (P = .034) cohorts.
  
  
  CONCLUSIONS
  Several genes considered prognostic in NSCLC showed significantly different expression in SCC and AC, and thus should be analyzed separately in these 2 subtypes for their prognostic significance. CSF1 is similarly expressed in SCC and AC, and portends a poor outcome in the entire group of patients with NSCLC, and in SCC and AC when considered separately.
authors.affiliation: Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdansk, Poland. Electronic address: mskrzypski@gumed.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Skrzypski
authors.forename: Rafał
authors.initials: R
authors.lastname: Dziadziuszko
authors.forename: Ewa
authors.initials: E
authors.lastname: Jassem
authors.forename: Amelia
authors.initials: A
authors.lastname: Szymanowska-Narloch
authors.forename: Grażyna
authors.initials: G
authors.lastname: Gulida
authors.forename: Robert
authors.initials: R
authors.lastname: Rzepko
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Jelitto-Górska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Marjański
authors.forename: Witold
authors.initials: W
authors.lastname: Rzyman
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D054642:Dual Specificity Phosphatase 6 / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D008222:Lymphokines; D050794:STAT1 Transcription Factor; C050979:monocyte-macrophage differentiation factor; D016173:Macrophage Colony-Stimulating Factor; C512478:EGFR protein, human; C581292:ERBB3 protein, human; D066246:ErbB Receptors; D020893:Receptor, ErbB-3; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); C517035:DUSP6 protein, human; D054642:Dual Specificity Phosphatase 6; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
keywords: Adjuvant chemotherapy; Gene expression; Lung adenocarcinoma; Prognosis; Reverse transcriptase-polymerase chain reaction; Squamous cell lung cancer