18F-FDG PET intensity correlates with a hypoxic gene signature and other oncogenic abnormalities in operable non-small cell lung cancer

Background18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is critical for staging non-small-cell lung cancer (NSCLC). While PET intensity carries prognostic significance, the genetic abnormalities associated with increased intensity remain unspecified.MethodsNSCLC samples (N = 34) from 1999 to 2011 for which PET data were available were identified from a prospectively collected tumor bank. PET intensity was classified as mild, moderate, or intense based on SUVmax measurement or radiology report. Associations between genome-wide expression (RNAseq) and PET intensity were determined. Associations with overall survival were then validated in two external NSCLC cohorts.ResultsOverall survival was significantly worse in patients with PET-intense (N = 11) versus mild (N = 10) tumors (p = 0.039). Glycolytic gene expression patterns were markedly similar between intense and mild tumors. Gene ontology analysis demonstrated significant enhancement of cell-cycle and proliferative processes in FDG-intense tumors (pMYC, NF-κB, and HIF-1. Using an external cohort of 25 tumors with PET and genomic profiling data, common genes and gene sets were validated for additional study (PHIF-1 expression did not correlate with poor survival in the NSCLC validation cohort (N = 442), established targets of hypoxia signaling (PLAUR, ADM, CA9) were significantly associated with poor overall survival.ConclusionsPET-intensity is associated with a variety of oncogenic alterations in operable NSCLC. Adjuvant targeting of these pathways may improve survival among patients with PET-intense tumors.