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| A Simple Two-Gene Molecular Prognostic Model for Adenocarcinoma of the Lung |
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Carolyn E. Reed1, Amanda Graham1, Michael B. Wallace2, Rana S. Hoda1, Andras Khoor2, Michael Mitas1; 1Surgery, Medical University of South Carolina, Charleston, SC; 2Mayo Clinic, Jacksonville, FL Objective: A significant number of patients recur after resection for stage I and II lung cancer. It is recognized that the ability of cells to gain metastatic potential is an intrinsic property of the tumor itself. We hypothesized that clinical outcome of resected early stage adenocarcinoma can be predicted by the expression of a few critically important genes (the ratio of "good gene" and "bad gene") as measured by quantitative real-time RT-PCR in formalin fixed paraffin-embedded (FFPE) primary tumors. Methods: previously identified 22 potential prognostic genes for the metastatic phenotype through cDNA microanalysis of four lung cancer cell lines and bioinformatics analysis. Expression levels of these genes were measured by real-time RT-PCR in FFPE primary adenocarcinoma (n=18) and bronchioloalveolar carcinoma (n=2) from patients who recurred within 2 years (n=9) and who did not recur (n=11). Results: ROC curve analysis was performed to establish prognostic values of single genes. The most informative gene, CK19, was then combined with remaining genes to determine if there was a particular pair that yielded high diagnostic accuracy. We found that the CK19/EpCAM2 gene ratio had the highest reproducible prognostic accuracy (AUC = 0.91; 95% CI = 0.69-0.99). The Kaplan Meier survival curve for the CK19/EpCAM2 gene ratio is shown in the figure. Conclusion: This preliminary study provides evidence that CK19/EpCAM2 ratio is a simple and accurate prognostic indicator of clinical outcome in early stage adenocarcinoma of the lung. Adjuvant therapy could be targeted to this high risk group if further ongoing validation studies from larger patient cohorts confirm the results. Back to Annual Meeting Back to Program Outline |
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