title: Array-comparative genomic hybridization reveals loss of SOCS6 is associated with poor prognosis in primary lung squamous cell carcinoma.
abstract: BACKGROUND
  Primary tumor recurrence commonly occurs after surgical resection of lung squamous cell carcinoma (SCC). Little is known about the genes driving SCC recurrence.
  
  
  METHODS
  We used array comparative genomic hybridization (aCGH) to identify genes affected by copy number alterations that may be involved in SCC recurrence. Training and test sets of resected primary lung SCC were assembled. aCGH was used to determine genomic copy number in a training set of 62 primary lung SCCs (28 with recurrence and 34 with no evidence of recurrence) and the altered copy number of candidate genes was confirmed by quantitative PCR (qPCR). An independent test set of 72 primary lung SCCs (20 with recurrence and 52 with no evidence of recurrence) was used for biological validation. mRNA expression of candidate genes was studied using qRT-PCR. Candidate gene promoter methylation was evaluated using methylation microarrays and Sequenom EpiTYPER analysis.
  
  
  RESULTS
  18q22.3 loss was identified by aCGH as being significantly associated with recurrence (p = 0.038). Seven genes within 18q22.3 had aCGH copy number loss associated with recurrence but only SOCS6 copy number was both technically replicated by qPCR and biologically validated in the test set. SOCS6 copy number loss correlated with reduced mRNA expression in the study samples and in the samples with copy number loss, there was a trend for increased methylation, albeit non-significant. Overall survival was significantly poorer in patients with SOCS6 loss compared to patients without SOCS6 loss in both the training (30 vs. 43 months, p = 0.023) and test set (27 vs. 43 months, p = 0.010).
  
  
  CONCLUSIONS
  Reduced copy number and mRNA expression of SOCS6 are associated with disease recurrence in primary lung SCC and may be useful prognostic biomarkers.
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, Queensland, Australia. bajee.sriram@uqconnect.edu.au
authors.forename: Krishna B
authors.initials: KB
authors.lastname: Sriram
authors.forename: Jill E
authors.initials: JE
authors.lastname: Larsen
authors.forename: Santiyagu M
authors.initials: SM
authors.lastname: Savarimuthu Francis
authors.forename: Casey M
authors.initials: CM
authors.lastname: Wright
authors.forename: Belinda E
authors.initials: BE
authors.lastname: Clarke
authors.forename: Edwina E
authors.initials: EE
authors.lastname: Duhig
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brown
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Ian A
authors.initials: IA
authors.lastname: Yang
authors.forename: Rayleen V
authors.initials: RV
authors.lastname: Bowman
authors.forename: Kwun M
authors.initials: KM
authors.lastname: Fong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000601:surgery; D002877:Chromosomes, Human / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D056726:Genetic Association Studies; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D015203:Reproducibility of Results; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C473085:SOCS6 protein, human; D050826:Suppressor of Cytokine Signaling Proteins