Boston - American Association for Thoracic Surgery

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89 TH ANNUAL MEETING MAY 9–MAY 13, 2009BOSTON, MASSACHUSETTSF11. MicroRNA Expression Profiles Predict Recurrence After Surgeryfor Stage 1 Non-Small Cell Lung CancerSai Yendamuri, 1 Steen Knudsen, 2 Todd L. Demmy, 1* Santosh Patnaik 11. Roswell Park Cancer Institute, Buffalo, NY, USA; 2. Medical PrognosisInstitute, Horsholm, DenmarkInvited Discussant: Virginia R. LitleOBJECTIVE: Surgery for stage 1 NSCLC has a significant recurrence rate. A toolfor predicting recurrence in these patients may direct adjuvant therapy to high riskpatients to maximize its risk benefit ratio. We studied the ability of an updatedmicroRNA (miRNA) microarray to predict recurrence in patients with pathologicstage 1 NSCLC.METHODS: Formalin fixed paraffin embedded (FFPE) tissue specimens from 79patients with pathologic stage 1 NSCLC were used for analysis. Tissue was deparaffinizedand miRNA extracted. After quality control assessments of the extractedRNA, hybridization was performed to a locked nucleic acid based array platformcontaining probes for all miRs in miRBase version 11. Data from the arrays werebackground corrected and Loess normalized. In a leave-one-out cross validation,miRNAs differentially expressed between patients with recurrence and patientswithout, were selected with a t-test, using a multiple testing correction leaving afalse discovery rate of 1%. The resulting miRNAs were subjected to Principal ComponentAnalysis. The five most important components trained a multivariate classifierusing the classification algorithms: K nearest neighbor, nearest centroid, neuralnetwork and support vector machine. The left out sample was predicted by majorityvote among the classification algorithms into “Good Prognosis” or “Poor Prognosis”.A Kaplan-Meier plot was prepared of the time to recurrence for the “Good Prognosis”and “Poor Prognosis” groups. A log-rank test for statistical significance of thedifference between the two groups was performed. As a leave one out cross validationwas performed, separate internal training and test sets were not created.* AATS Member138
AMERICAN ASSOCIATION FOR THORACIC SURGERYRESULTS: Of 79 samples, 78 samples passed the quality control conditions forhybridization. Data analysis performed as detailed above led to a model containingover 100 miRNA included in the five principal components. This model predictedoutcome in a statistically significant fashion (Figure 1). Median time to recurrencein “Good Prognosis” tumors had not been reached, whereas the median time torecurrence in “Poor Prognosis” tumors was 22 months (p < 0.01).CONCLUSION: This miRNA microarray profile predicts recurrence after surgeryfor stage 1 NSCLC and deserves validation by datasets from other institutions.Furthermore, ease in the handling of input material (avoiding frozen tissue) andstability of miRNA to degradation makes this platform more practical thanmRNA-based technologies in all clinical environments.TUESDAYMorning139
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AATS FUTURE MEETINGSMay 1-5, 2010Me
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