Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI
| Autor: | Durga Udayakumar, Alberto Diaz de Leon, Ananth J. Madhuranthakam, Yin Xi, DK Dwivedi, James Brugarolas, Payal Kapur, Ling Cai, Yue Zhang, Ralph J. DeBerardinis, Jeffrey G. McDonald, Zeping Hu, Hyeonwoo Kim, Michael Fulkerson, Jin Ye, Ivan Pedrosa, Takeshi Yokoo, Andrea Pavia-Jimenez, Eun Young Kho, Jeffrey A. Cadeddu, Matthew A. Mitsche, Qing Yuan, Ivan E. Dimitrov, Vitaly Margulis, Robert E. Lenkinski |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Cholesterol business.industry Lipid metabolism General Medicine Carbohydrate metabolism medicine.disease 3. Good health 03 medical and health sciences Clear cell renal cell carcinoma chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Metabolomics chemistry In vivo 030220 oncology & carcinogenesis Lipidomics medicine Biomarker (medicine) Clinical Medicine business |
| Zdroj: | JCI Insight. 2 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.94278 |
| Popis: | 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, ρ = 0.79), spectrometric triglycerides (ρ = 0.56) and cholesterol (ρ = 0.47); it showed negative correlation with free fatty acids (ρ = -0.44) and phospholipids (ρ = -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. FUNDING NIH R01CA154475 (YZ, MF, PK, IP), NIH P50CA196516 (IP, JB, RJD, JAC, PK), Welch Foundation I-1832 (JY), and NIH P01HL020948 (JGM). |
| Databáze: | OpenAIRE |
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