Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma
Journal article, 2016

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.

Author

Francesco Gatto

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

N. Volpi

Universita Degli Studi Di Modena E Reggio Emilia

H. Nilsson

Lund University

Intawat Nookaew

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

M. Maruzzo

IRCCS Istituto Oncologico Veneto IOV

A. Roma

IRCCS Istituto Oncologico Veneto IOV

M. E. Johansson

Lund University

Ulrika Stierner

University of Gothenburg

Sven Lundstam

University of Gothenburg

U. Basso

IRCCS Istituto Oncologico Veneto IOV

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Cell Reports

2211-1247 (ISSN)

Vol. 15 8 1822-1836

Subject Categories

Cell Biology

Areas of Advance

Life Science Engineering (2010-2018)

DOI

10.1016/j.celrep.2016.04.056

PubMed

27184840

More information

Latest update

9/6/2018 1