From Moffitt: Malignancy-Risk Gene Signature in Lung Cancer

http://www.ncbi.nlm.nih.gov/pubmed/22157961

J Natl Cancer Inst. 2011 Dec 8. [Epub ahead of print]
Prognostic and Predictive Value of a Malignancy-Risk Gene Signature in Early-Stage Non-Small Cell Lung Cancer.
Chen DT, Hsu YL, Fulp WJ, Coppola D, Haura EB, Yeatman TJ, Cress WD.
Source
Affiliations of authors: Department of Biostatics (D-TC, WJF), Department of Pathology (DC), Department of Molecular Oncology (EBH, WDC), Department of Surgery and Interdisciplinary Oncology (TJY), Moffitt Cancer Center & Research Institute, Tampa, FL; Department of Applied Mathematics and Institute of Statistics, National Chung Hsing University, Taiwan (Y-LH).

Abstract
Background
The malignancy-risk gene signature is composed of numerous proliferative genes and has been applied to predict breast cancer risk. We hypothesized that the malignancy-risk gene signature has prognostic and predictive value for early-stage non-small cell lung cancer (NSCLC) patients.

Methods
The ability of the malignancy-risk gene signature to predict overall survival (OS) of early-stage NSCLC patients was tested using a large NSCLC microarray dataset from the Director's Challenge Consortium (n = 442) and two independent NSCLC microarray datasets (n = 117 and 133, for the GSE13213 and GSE14814 datasets, respectively). An overall malignancy-risk score was generated by principal component analysis to determine the prognostic and predictive value of the signature. An interaction model was used to investigate a statistically significant interaction between adjuvant chemotherapy (ACT) and the gene signature. All statistical tests were two-sided.

Results
The malignancy-risk gene signature was statistically significantly associated with OS (P < .001) of NSCLC patients. Validation with the two independent datasets demonstrated that the malignancy-risk score had prognostic and predictive values: Of patients who did not receive ACT, those with a low malignancy-risk score had increased OS compared with a high malignancy-risk score (P = .007 and .01 for the GSE13212 and GSE14814 datasets, respectively), indicating a prognostic value; and in the GSE14814 dataset, patients receiving ACT survived longer in the high malignancy-risk score group (P = .03), and a statistically significant interaction between ACT and the signature was observed (P = .02).

Conclusions
The malignancy-risk gene signature was associated with OS and was a prognostic and predictive indicator. The malignancy-risk gene signature could be useful to improve prediction of OS and to identify those NSCLC patients who will benefit from ACT.