Prognostic Gene Expression Signature for Squamous Cell Carcinoma of Lung.
Summary of "Prognostic Gene Expression Signature for Squamous Cell Carcinoma of Lung."
PURPOSE:
To identify and validate a gene expression signature for squamous cell carcinoma of the lung (SQCC). EXPERIMENTAL
DESIGN:
A published microarray dataset from 129 SQCC patients was used as a training set to identify the minimal gene set prognostic signature. This was selected using the MAximizing R Square Algorithm (MARSA), a novel heuristic signature optimization procedure based on goodness-of-fit (R square). The signature was tested internally by leave-one-out-cross-validation (LOOCV), and then externally in 3 independent public lung cancer microarray datasets: 2 datasets of NSCLC and one of adenocarcinoma (ADC) only. Quantitative-PCR (qPCR) was used to validate the signature in a fourth independent SQCC cohort.
RESULTS:
A 12-gene signature that passed the internal LOOCV validation was identified. The signature was independently prognostic for SQCC in two NSCLC datasets (total n=223) but not in ADC. The lack of prognostic significance in ADC was confirmed in the Director's challenge ADC dataset (n=442). The prognostic significance of the signature was validated further by qPCR in another independent cohort containing 62 SQCC samples (HR=3.76, 95% CI 1.10-12.87, p=0.035).
CONCLUSIONS:
We have identified a novel 12-gene prognostic signature specific for SQCC and demonstrated the effectiveness of MARSA to identify prognostic gene expression signatures.
Affiliation
Applied Molecular Oncology, Ontario Cancer Institute,University of Toronto.
Journal Details
This article was published in the following journal.
Name: Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1078-0432
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20739434
- DOI: http://dx.doi.org/10.1158/1078-0432.CCR-10-0612
Medical and Biotech [MESH] Definitions
Carcinoma, Non-small-cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
Carcinoma, Squamous Cell
A carcinoma derived from stratified squamous epithelium. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
Carcinoma, Bronchogenic
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.
Carcinoma, Adenosquamous
A mixed adenocarcinoma and squamous cell or epidermoid carcinoma.
Small Cell Lung Carcinoma
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).
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