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Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma

Gatto, Francesco; Volpi, Nicola; Nilsson, Helén LU ; Nookaew, Intawat; Maruzzo, Marco; Roma, Anna; Johansson, Martin E. LU ; Stierner, Ulrika; Lundstam, Sven and Basso, Umberto, et al. (2016) In Cell Reports 15(8). p.1822-1836
Abstract

Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the... (More)

Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis.

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Cell Reports
volume
15
issue
8
pages
15 pages
publisher
Cell Press
external identifiers
  • Scopus:84966671361
ISSN
2211-1247
DOI
10.1016/j.celrep.2016.04.056
language
English
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yes
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a2546337-64a5-4fb1-b3d7-16ca04f25f15
date added to LUP
2016-09-27 14:25:36
date last changed
2016-11-17 12:18:56
@misc{a2546337-64a5-4fb1-b3d7-16ca04f25f15,
  abstract     = {<p>Metabolic reprogramming is a hallmark of clear cell renal cell carcinoma (ccRCC) progression. Here, we used genome-scale metabolic modeling to elucidate metabolic reprogramming in 481 ccRCC samples and discovered strongly coordinated regulation of glycosaminoglycan (GAG) biosynthesis at the transcript and protein levels. Extracellular GAGs are implicated in metastasis, so we speculated that such regulation might translate into a non-invasive biomarker for metastatic ccRCC (mccRCC). We measured 18 GAG properties in 34 mccRCC samples versus 16 healthy plasma and/or urine samples. The GAG profiles were distinctively altered in mccRCC. We derived three GAG scores that distinguished mccRCC patients with 93.1%-100% accuracy. We validated the score accuracies in an independent cohort (up to 18 mccRCC versus nine healthy) and verified that the scores normalized in eight patients with no evidence of disease. In conclusion, coordinated regulation of GAG biosynthesis occurs in ccRCC, and non-invasive GAG profiling is suitable for mccRCC diagnosis.</p>},
  author       = {Gatto, Francesco and Volpi, Nicola and Nilsson, Helén and Nookaew, Intawat and Maruzzo, Marco and Roma, Anna and Johansson, Martin E. and Stierner, Ulrika and Lundstam, Sven and Basso, Umberto and Nielsen, Jens},
  issn         = {2211-1247},
  language     = {eng},
  month        = {05},
  number       = {8},
  pages        = {1822--1836},
  publisher    = {ARRAY(0x8ac47f0)},
  series       = {Cell Reports},
  title        = {Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma},
  url          = {http://dx.doi.org/10.1016/j.celrep.2016.04.056},
  volume       = {15},
  year         = {2016},
}