Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer

摘要

Although ¹⁸F-2-fluoro-2-deoxyglucose (FDG) uptake during positron emission tomography (PET) predicts post-surgical outcome in patients with non-small-cell lung cancer (NSCLC), the biologic basis for this observation is not fully understood. Here we analyzed 25 tumors from NSCLC patients to identify tumor ¹⁸F-FDG PET uptake features associated with gene expression signatures and survival. Fourteen quantitative PET imaging features describing FDG uptake were correlated with gene expression for single genes and co-expressed gene clusters (metagenes). For each FDG uptake feature, an associated metagene signature was derived and a prognostic model was identified in an external and tested in a validation cohort of NSCLC patients. Four of 8 single genes associated with FDG uptake (LY6E, RNF149, MCM6, FAP) were also associated with survival. The most prognostic metagene signature was associated with a multivariate FDG uptake feature (SUVmax, SUVvariance and SUVPCA2), each highly associated with survival in the external (HR 5.87, confidence interval [CI] 2.49-13.8) and validation (HR 6.12, CI 1.08-34.8) cohorts, respectively. Cell cycle, proliferation, death, and self-recognition pathways were altered in this radiogenomic profile. Together, our findings suggest that leveraging tumor genomics with an expanded collection of PET-FDG imaging features may enhance our understanding of FDG uptake as an imaging biomarker beyond its association with glycolysis.