A Five-Gene and Corresponding Protein Signature for Stage-I Lung Adenocarcinoma Prognosis

Purpose: Identification of effective markers for outcome is expected to improve the clinical management of non-small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis. Experimental Design: Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffin-embedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs). Results: The survival of all-stages (P < 0.001, HR = 2.0) or stage-I (P < 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P < 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P < 0.001, HR - 3.6; stage-I, P < 0.001, HR - 3.5; stage-IB, P < 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P < 0.001, HR = 7.2) in lung adenocarcinoma patients. Conclusions: Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy. Clin Cancer Res; 17(6); 1490-501. (C) 2010 AACR.