Value of global metabolomics in association with diagnosis and clinicopathological factors of renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) is a malignant tumor that currently lacks clinically useful biomarkers indicative of early diagnosis or disease status. RCC has commonly been diagnosed based on imaging results. Metabolomics offers a potential technology for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. We aimed to identify metabolites associated with early diagnosis and clinicopathological factors in RCC using global metabolomics (G‐Met). Tumor and nontumor tissues were sampled from 20 cases of surgically resected clear cell RCC. G‐Met was performed by liquid chromatography mass spectrometry and important metabolites specific to RCC were analyzed by multivariate statistical analysis for cancer diagnostic ability based on area under the curve (AUC) and clinicopathological factors (tumor volume, pathological T stage, Fuhrman grade, presence of coagulation necrosis and distant metastasis). We identified 58 metabolites showing significantly increased levels in tumor tissues, 34 of which showed potential early diagnostic ability (AUC >0.8), but 24 did not discriminate between tumor and nontumor tissues (AUC ≤0.8). We recognized 6 pathways from 9 metabolites with AUC >0.8 and 7 pathways from 10 metabolites with AUC ≤0.8 about malignant status. Clinicopathological factors involving malignant status correlated significantly with metabolites showing AUC ≤0.8 (p = 0.0279). The tricarboxylic acid cycle (TCA) cycle, TCA cycle intermediates, nucleotide sugar pathway and inositol pathway were characteristic pathways for the malignant status of RCC. In conclusion, our study found that metabolites and their pathways allowed discrimination between early diagnosis and malignant status in RCC according to our G‐Met protocol.

Metabolomic Analysis to Elucidate Mechanisms of Sunitinib Resistance in Renal Cell Carcinoma

“…We previously investigated metabolites of clear cell RCC (ccRCC) by using our global metabolomics (G-Met) protocol in tissue samples [16,17]. Pathways of metabolites such as glutathione, tryptophan and glycolysis were associated with diagnosis and malignant status.…”

UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma

“…In addition, they also discovered that in metastatic RCC, lipid metabolism was upregulated, which may be related to tumour progression [26]. In some other studies, metabolites of carnitine metabolism, which are responsible for the transportation of fatty acids into the mitochondria, have been found to be increased in high-grade tumour tissues, blood serum or urine [27–29], which may be a consequence of improved fatty acid β-oxidation to sustain higher rates of cell division and growth.…”

UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma

“…Besides, they also discovered that in metastatic RCC, the lipid metabolism was upregulated obviously, which may be related to the tumor progression 26 . In some other researches, metabolites of carnitine metabolism, which are responsible for the transportation of fatty acid into the mitochondria, have been found to be increased in high-grade tumor tissues, blood serum or urine [27][28][29] , which may be a consequence of improved fatty acid β-oxidation to sustain higher rates of cell division and growth.…”