title: Application of ex vivo (1)H NMR metabonomics to the characterization and possible detection of renal cell carcinoma metastases.
abstract: OBJECTIVE
  Renal cell carcinoma (RCC) is the most prevalent malignancy of the kidney. Its survival rates are very low since most of patients develop metastases beyond the kidney at the time of diagnosis. Early detection is currently by far the most promising approach to reduce RCC mortality. Metabolic alterations have been suggested to have a crucial role in cancer development. Metabonomics can present a holistic picture of the metabolites alterations and provide biomarkers that could revolutionize disease characterization and detection.
  
  
  METHODS
  Ex vivo (1)H NMR spectra of tumors and the paired adjacent tissues obtained from living patients with RCC were recorded and analyzed using multivariate statistical techniques combined with quantitative statistical analyses.
  
  
  RESULTS
  In the present study, we showed that the metabonomes of RCC, either with or without metastases, differ markedly from those of their adjacent tissues. Besides, the RCC patients with metastases can be distinctly differentiated from those without metastases. Metabolic perturbations arising from malignant transformations were also systematically characterized. Compared to the adjacent tissues, RCC tumors had elevated levels of lactate, glutamate, pyruvate, glutamine, and creatine, but decreased levels of acetate, malate, and amino acids including valine, alanine, and aspartate.
  
  
  CONCLUSIONS
  Systemic changes in metabolite concentrations are most likely the result of cells switching to glycolysis to maintain energy homeostasis. The results suggest that metabonomics may also facilitate the discovery of novel cancer biomarkers and allows the stratification of tumors under different pathophysiological conditions, which might be a valuable future tool for RCC detection and possibly other cancers.
authors.affiliation: School of Pharmacy, and Radiology Department of the Second Affiliated Hospital, Wenzhou Medical College, Wenzhou, People's Republic of China. gaohc27@gmail.com
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
authors.forename: Baijun
authors.initials: B
authors.lastname: Dong
authors.forename: Jianmin
authors.initials: J
authors.lastname: Jia
authors.forename: Huan
authors.initials: H
authors.lastname: Zhu
authors.forename: Chengfeng
authors.initials: C
authors.lastname: Diao
authors.forename: Zhihan
authors.initials: Z
authors.lastname: Yan
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D053858:Metabolic Networks and Pathways / Q000502:physiology; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D011522:Protons; D014020:Tissue Extracts / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D011522:Protons; D014020:Tissue Extracts