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Radiogenomic Analysis Demonstrates Associations between 18F-Fluoro-2-Deoxyglucose PET, Prognosis, and Epithelial-Mesenchymal Transition in Non–Small Cell Lung Cancer1

Purpose:
To investigate whether non–small cell lung cancer (NSCLC) tumors that express high normalized maximum standardized uptake value (SUVmax) are associated with a more epithelial-mesenchymal transition (EMT)–like phenotype.

Materials and Methods:
In this institutional review board–approved study, a public NSCLC data set that contained fluorine 18 (18F) fluoro-2-deoxyglucose positron emission tomography (PET) and messenger RNA ex-pression profile data (n = 26) was obtained, and patients were categorized on the basis of measured normalized SUVmax values. Significance analysis of microarrays was then used to create a radiogenomic signature. The prognostic ability of this signature was assessed in a second independent data set that consisted of clinical and messenger RNA expression data (n = 166). Signature concordance with EMT was evaluated by means of validation in a publicly available cell line data set. Finally, by establishing an in vi-tro EMT lung cancer cell line model, an attempt was made to sub-stantiate the radiogenomic signature with quantitative polymerase chain reaction, and functional assays were performed, including Western blot, cell migration, glucose transporter, and hexokinase assays (paired t test), as well as pharmacologic assays against chemotherapeutic agents (half-maximal effective concentration).

Results:
Differential expression analysis yielded a 14-gene radiogenomic signature (P , .05, false discovery rate [FDR] , 0.20), which was confirmed to have differences in disease-specific survival (log-rank test, P = .01). This signature also significantly overlapped with published EMT cell line gene expression data (P , .05, FDR , 0.20). Finally, an EMT cell line model was established, and cells that had undergone EMT differentially expressed this signature and had significantly different EMT protein expres-sion (P , .05, FDR , 0.20), cell migration, glucose uptake, and hexokinase activity (paired t test, P , .05). Cells that had undergone EMT also had enhanced chemotherapeutic resis-tance, with a higher half-maximal effective concentration than that of cells that had not undergone EMT (P , .05).

Conclusion:
Integrative radiogenomic analysis demonstrates an association between increased normalized 18F fluoro-2-deoxyglucose PET SUVmax, outcome, and EMT in NSCLC.

© RSNA, 2016

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Yamamoto S., Du L., Korn R.L., Jamshidi N., Burnette B.L., & Kuo MD. “Radiogenomic Analysis Demonstrates Associations between 18F-Fluoro-2-Deoxyglucose PET, Prognosis, and Epithelial-Mesenchymal Transition in Non–Small Cell Lung Cancer1.” Radiology, 280:1, (2016).

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