Application of ex vivo 1H NMR metabonomics to the characterization and possible detection of renal cell carcinoma metastases

Gao, Hongchang; Dong, Baijun; Jia, Jianmin; Zhu, Hengyue; Diao, Chengfeng; Yan, Zhihan; Huang, Yiran; Li, Xiaokun

doi:10.1007/s00432-011-1134-6

Cited by 54 publications

(51 citation statements)

References 27 publications

(28 reference statements)

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“…In the particular case of RCC, metabolomics-based studies have already been successfully applied to paired cancer and normal renal tissue2930313233, showing its potential to discriminate cancer and normal tissue as well as study RCC progression and aggressiveness. A lack of correspondence between altered pathways proposed by genomics and metabolomics was observed highlighting that genetics only describes part of the pathophysiologic metabolic rearrangements of RCC29.…”

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confidence: 99%

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma

Monteiro

Barros

Pinto

et al. 2016

Sci Rep

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RCC usually develops and progresses asymptomatically and, when detected, it is frequently at advanced stages and metastatic, entailing a dismal prognosis. Therefore, there is an obvious demand for new strategies enabling an earlier diagnosis. The importance of metabolic rearrangements for carcinogenesis unlocked a new approach for cancer research, catalyzing the increased use of metabolomics. The present study aimed the NMR metabolic profiling of RCC in urine samples from a cohort of RCC patients (n = 42) and controls (n = 49). The methodology entailed variable selection of the spectra in tandem with multivariate analysis and validation procedures. The retrieval of a disease signature was preceded by a systematic evaluation of the impacts of subject age, gender, BMI, and smoking habits. The impact of confounders on the urine metabolomics profile of this population is residual compared to that of RCC. A 32-metabolite/resonance signature descriptive of RCC was unveiled, successfully distinguishing RCC patients from controls in principal component analysis. This work demonstrates the value of a systematic metabolomics workflow for the identification of robust urinary metabolic biomarkers of RCC. Future studies should entail the validation of the 32-metabolite/resonance signature found for RCC in independent cohorts, as well as biological validation of the putative hypotheses advanced.

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confidence: 99%

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma

Monteiro

Barros

Pinto

et al. 2016

Sci Rep

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“…Further comparisons comprised three patients with other tumor types (benign or metastasized from other cancer types) and eight of the patients after having undergone nephrectomy. The results revealed lower levels of lysophosphatidylcholines (LPC) in RCC patients, compared with Reproduced with permission from [53] © Springer (2012). controls (with some differences in LPC levels being noted between males and females), and lower phosphatidylcholine (PC) levels, observed for female patients in particular.…”

Section: Human Biofluidsmentioning

confidence: 93%

“…No NMR metabolomics of renal cancer: an overview Special Report details were advanced in this study on the biochemical interpretation of results. A more recent report compared methanol/chloroform/water tissue extracts obtained for 31 RCC patients, comprising 11 subjects at an advanced stage of the disease (with metastases, stages T3 and T4) and the remaining 20 considered low-grade (without metastases, stages T1 and T2) [53]. Figure 2 shows representative 1 H NMR spectra of extracts obtained from adjacent tissue, low-grade and advanced RCC tumors.…”

Section: Analysis Of Tissue Extractsmentioning

confidence: 98%

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Nmr Metabolomics of Renal Cancer: an Overview

et al. 2015

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This paper reviews the use of NMR metabolomics for the metabolic characterization of renal cancer. The existing challenges in the clinical management of this disease are first presented, followed by a brief introduction to the metabolomics approach, in the context of cancer research. A subsequent review of the literature on NMR metabolic studies of renal cancer reveals that the subject has been clearly underdeveloped, compared with other types of cancer, particularly regarding cultured cells and tissue analysis. NMR analysis of biofluids has focused on blood (plasma or serum) metabolomics, comprising no account of studies on human urine, in spite of its noninvasiveness and physiological proximity to the affected organs. Finally, some areas of potential future development are identified.

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“…The 1 H NMR experiments and PLS-DA analysis were performed as described previously [21, 22]. The concentrations of target metabolites were quantified from the spectra using trimethylsilyl-propionic-2,2,3,3d 4 -acid (TSP) as the internal reference and normalized to the weight of the tissues, which are shown in the unit of mmol/kg wet tissue weight.…”

Section: Methodsmentioning

confidence: 99%

SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis

et al. 2016

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Metabolic shift toward aerobic glycolysis is a fundamental element contributing to the development and progression of clear cell renal cell carcinoma (ccRCC). We and others previously observed enhanced glycolysis and diminished tricarboxylic acid (TCA) cycle activity in ccRCC tissue. Here, by integrated gene expression and metabolomic analyses of 36 matched pairs of tumor and adjacent normal tissues, we showed that expression of Sentrin/SUMO-specific protease 1 (SENP1) is positively associated with glycolysis levels in ccRCC. Moreover, SENP1 knockdown in RCC4/VHL cells downregulated expression of key glycolytic enzymes under normoxic and hypoxic conditions and inhibited cell proliferation under hypoxic conditions, possibly due to ineffective deSUMOylation and stablization of Hif-1α related to the SENP-1 deficiency. Finally, SENP1 expression correlated positively with tumor pathological grade and was an indicator of poor overall survival and advanced tumor progression in ccRCC. Altered VHL gene function is found in 60–90% ccRCC cases of ccRCC, but therapies targeting VHL-related signaling pathways have been ineffective, spurring exploration of alternative pathological signaling events. Our results provide a possible mechanistic explanation for the role of SENP1 in the initiation and development of ccRCC with normal VHL activity, and identifies SENP1 as a potential treatment target for the disease.

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Application of ex vivo 1H NMR metabonomics to the characterization and possible detection of renal cell carcinoma metastases

Cited by 54 publications

References 27 publications

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma

Nuclear Magnetic Resonance metabolomics reveals an excretory metabolic signature of renal cell carcinoma

Nmr Metabolomics of Renal Cancer: an Overview

SENP1 promotes proliferation of clear cell renal cell carcinoma through activation of glycolysis

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