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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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. 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. Adju-vant targeting of these pathways may improve survival among patients with PET-intense tumors.

Original languageEnglish (US)
Article numbere0199970
JournalPloS one
Volume13
Issue number7
DOIs
StatePublished - Jul 2018

Funding

This work was supported in part by the American Association for Thoracic Surgery (AATS, www.aats.org) and the American Federation for Aging Research (AFAR, www.afar.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Nair et al. for sharing their radiogenomic data.

ASJC Scopus subject areas

  • General

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