Abstract
Background18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated.MethodsCorrelations between EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients. Molecular causal relationships between EGFR or KRAS mutation status and glucose metabolism were then elucidated in 62 lung adenocarcinomas using cap analysis of gene expression (CAGE), a method to determine and quantify the transcription initiation activities of mRNA across the genome.ResultsEGFR and KRAS mutations were detected in 334 (46%) and 83 (11%) of the 734 lung adenocarcinomas, respectively. The remaining 317 (43%) patients had wild-type tumors for both genes. EGFR mutations were more frequent in tumors with lower SUVmax. In contrast, no relationship was noted between KRAS mutation status and SUVmax. CAGE revealed that 4 genes associated with glucose metabolism (GPI, G6PD, PKM2, and GAPDH) and 5 associated with the cell cycle (ANLN, PTTG1, CIT, KPNA2, and CDC25A) were positively correlated with SUVmax, although expression levels were lower in EGFR-mutated than in wild-type tumors. No similar relationships were noted with KRAS mutations.ConclusionsEGFR-mutated adenocarcinomas are biologically indolent with potentially lower levels of glucose metabolism than wild-type tumors. Several genes associated with glucose metabolism and the cell cycle were specifically down-regulated in EGFR-mutated adenocarcinomas.
Highlights
Driver oncogene mutations are being discovered at a rapid pace
Correlation of epidermal growth factor receptor (EGFR) or Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status with FDG uptake in lung adenocarcinoma we retrospectively reviewed 734 adenocarcinoma patients who underwent 18F-FDG positron emission tomography (PET)-CT scanning within 2 months before surgery and whose surgically resected specimens were examined for EGFR and KRAS mutations
Several genes associated with glucose metabolism or the cell cycle were down-regulated in EGFR m+ adenocarcinomas
Summary
Driver oncogene mutations are being discovered at a rapid pace. The somatic mutations in epidermal growth factor receptor (EGFR) and v-Ki-ras Kirsten rat sarcoma viral oncogene homolog (KRAS) are the most frequently found in lung adenocarcinomas. The presence of an EGFR mutation is the most important predictor of the efficacy of EGFR tyrosine kinase inhibitors (TKIs) [1, 2]. KRAS mutations are a useful biomarker of EGFR-TKI resistance [3]. It is important to understand the occurrence of EGFR and KRAS mutations when deciding the initial treatment for lung cancer. Non-invasive methods to estimate the probability of the EGFR/KRAS mutation status are helpful in clinical practice. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated
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