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Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI
Yue Zhang1, Durga Udayakumar1,2, Ling Cai3,4
1Radiology.
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).
Insights
Quantitative MRI can noninvasively predict lipid metabolism changes in clear cell renal cell carcinoma (ccRCC). This method may help assess tumor aggressiveness before surgery.
Area of Science:
- Oncology
- Radiology
- Metabolomics
Background:
- Dysregulated lipid and glucose metabolism are hallmarks of clear cell renal cell carcinoma (ccRCC) progression.
- Assessing these metabolic changes in ccRCC is challenging due to tumor heterogeneity.
- Noninvasive quantitative MRI offers a potential solution for whole-tumor metabolic assessment.
Purpose of the Study:
- To evaluate a noninvasive quantitative MRI method for predicting metabolic alterations in ccRCC.
- To correlate MRI-derived lipid quantification with tissue-based metabolomic analysis.
- To assess the potential of MRI as a biomarker for ccRCC aggressiveness.
Main Methods:
- Dixon-based MRI was used for in vivo quantification of fat fraction (FF) in 45 primary ccRCCs.
- MRI measures were correlated with mass spectrometry-based lipidomics and metabolomics from surgically resected tumor samples.
- Inter- and intratumoral heterogeneity of lipid accumulation was analyzed.
Main Results:
- In vivo tumor FF positively correlated with histologic fat content, triglycerides, and cholesterol.
- Tumor FF negatively correlated with free fatty acids and phospholipids.
- More aggressive tumors (ISUP grade 4) showed reduced lipid accumulation, indicating metabolic reprogramming.
Conclusions:
- Noninvasive quantitative Dixon-based MRI is a valid biomarker for reprogrammed lipid metabolism in ccRCC.
- This MRI technique can predict tumor aggressiveness before surgical intervention.
- MRI-based lipid quantification aids in understanding ccRCC metabolic heterogeneity.
