Journal
JCI INSIGHT
Volume 2, Issue 15, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.94278
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Funding
- NIH [R01CA154475, P50CA196516, P01HL020948]
- Welch Foundation [I-1832]
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BACKGROUND. Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue-based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS. We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry-based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery. RESULTS. In vivo tumor FF showed statistically significant (P < 0.0001) positive correlation with histologic fat content (Spearman correlation coefficient, rho = 0.79), spectrometric triglycerides (rho = 0.56) and cholesterol (rho = 0.47); it showed negative correlation with free fatty acids (rho = -0.44) and phospholipids (rho = -0.65). We observed both inter-and intratumoral heterogeneity in lipid accumulation within the same tumor grade, whereas most aggressive tumors (International Society of Urological Pathology [ISUP] grade 4) exhibited reduced lipid accumulation. Cellular metabolites in tumors were altered compared with adjacent renal parenchyma. CONCLUSION. Our results support the use of noninvasive quantitative Dixon-based MRI as a biomarker of reprogrammed lipid metabolism in ccRCC, which may serve as a predictor of tumor aggressiveness before surgical intervention.
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