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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).    Conclusion  Reduced copy number and mRNA expression of  SOCS6  are associated with disease recurrence in primary lung SCC and may be useful prognostic biomarkers.

Array-Comparative Genomic Hybridization Reveals Loss of SOCS6 Is Associated with Poor Prognosis in Primary Lung Squamous Cell Carcinoma