PLoS ONE (Jan 2018)

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

  • Brendan T Heiden,
  • Guoan Chen,
  • Matthew Hermann,
  • Richard K J Brown,
  • Mark B Orringer,
  • Jules Lin,
  • Andrew C Chang,
  • Philip W Carrott,
  • William R Lynch,
  • Lili Zhao,
  • David G Beer,
  • Rishindra M Reddy

DOI
https://doi.org/10.1371/journal.pone.0199970
Journal volume & issue
Vol. 13, no. 7
p. e0199970

Abstract

Read online

BACKGROUND:18F-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. METHODS:NSCLC 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. RESULTS:Overall 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 (p<0.001). Gene set enrichment analysis (GSEA) suggested associations between PET-intensity and canonical oncogenic signaling pathways including MYC, 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 (P<0.05). Of these common gene sets, 20% were associated with hypoxia or HIF-1 signaling. While HIF-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. CONCLUSIONS:PET-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.