Retrospective and prospective validation of a 33-gene signature to predict recurrence of lung cancer after surgery.

We developed a 33-gene signature that is strongly correlated to the time to recurrence in non-small cell lung cancer (NSCLC). The signature was validated retrospectively in 5 cohorts of 972 NSCLC patients and in one prospective study of 111 NSCLC Stage IA patients. In all cohorts, and all stages of the disease, the signature identified a rare, aggressive tumor type that had a high proportion of recurrence after surgery and a median survival of 35 months (95% C.I.: 19-58). This tumor type forms a separate cluster in an analysis of the expression of the 33 genes in patient tumors. The signature is associated with cellular processes required by rapidly growing and spreading tumors: cell migration and invasion, vascularization, and response to hypoxia. The signature also identifies patients with good prognosis (median survival 114 months, (95% C.I.: 85-160), and intermediate prognosis (median survival 61 months (95% C. I.: 50-73). The signature is quite robust and works on tumor samples archived in RNAlater, Tissue-Tek, or formalin-fixed and paraffin embedded.

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