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Carcinogenesis Advance Access originally published online on November 1, 2006
Carcinogenesis 2007 28(3):760-766; doi:10.1093/carcin/bgl207
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Expression profiling defines a recurrence signature in lung squamous cell carcinoma

Jill Everland Larsen1,3,*, Sandra Jane Pavey3,4, Linda Hazel Passmore1, Rayleen Bowman3, Belinda Edith Clarke2, Nicholas Kim Hayward3,4 and Kwun Meng Fong1,3

1 Department of Thoracic Medicine Brisbane, 4032, Australia
2 Department of Pathology, The Prince Charles Hospital Brisbane, 4032, Australia
3 School of Medicine, University of Queensland Herston, 4006, Australia
4 Human Genetics Laboratory, Queensland Institute of Medical Research Herston, 4006, Australia

*To whom correspondence should be addressed. Tel: +61 7 3139 4110; Email: Jill_E_Larsen{at}health.qld.gov.au

Lung cancer remains the leading cause of cancer death worldwide. Overall 5-year survival is ~10–15% and despite curative intent surgery, treatment failure is primarily due to recurrent disease. Conventional prognostic markers are unable to determine which patients with completely resected disease within each stage group are likely to relapse. To identify a gene signature associated with recurrent squamous cell carcinoma (SCC) of lung, we analyzed primary tumor gene expression for a total of 51 SCCs (Stages I–III) on 22 323 element microarrays, comparing expression profiles for individuals who remained disease-free for a minimum of 36 months with those from individuals whose disease recurred within 18 months of complete resection. Cox proportional hazards modeling with leave-one-out cross-validation identified a 71-gene signature capable of predicting the likelihood of tumor recurrence and a 79-gene signature predictive for cancer-related death. These two signatures were pooled to generate a 111-gene signature which achieved an overall predictive accuracy for disease recurrence of 72% (77% sensitivity, 67% specificity) in an independent set of 58 (Stages I–III SCCs). This signature also predicted differences in survival [log-rank P = 0.0008; hazard ratio (HR), 3.8; 95% confidence interval (CI), 1.6–8.7], and was superior to conventional prognostic markers such as TNM stage or N stage in predicting patient outcome. Genome-wide profiling has revealed a distinct gene-expression profile for recurrent lung SCC which may be clinically useful as a prognostic tool.

Abbreviations: AC, adenocarcinoma; LCC, large cell carcinoma; NSCLC, non-small cell lung carcinoma; Rec(–), clinically disease-free for atleast 36 months following surgery; Rec(+), recurrent; SCC, squamous cell carcinoma.

Received July 19, 2006; revised October 15, 2006; accepted October 20, 2006.


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