Glycosaminoglycan Profiling in Patients' Plasma and Urine Predicts the Occurrence of Metastatic Clear Cell Renal Cell Carcinoma
Artikel i vetenskaplig tidskrift, 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.

Författare

Francesco Gatto

Chalmers, Biologi och bioteknik, Systembiologi

N. Volpi

Universita Degli Studi Di Modena E Reggio Emilia

H. Nilsson

Lunds universitet

Intawat Nookaew

Chalmers, Biologi och bioteknik, Systembiologi

M. Maruzzo

IRCCS Istituto Oncologico Veneto IOV

A. Roma

IRCCS Istituto Oncologico Veneto IOV

M. E. Johansson

Lunds universitet

Ulrika Stierner

Göteborgs universitet

Sven Lundstam

Göteborgs universitet

U. Basso

IRCCS Istituto Oncologico Veneto IOV

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Cell Reports

22111247 (eISSN)

Vol. 15 8 1822-1836

Ämneskategorier

Cellbiologi

Styrkeområden

Livsvetenskaper och teknik (2010-2018)

DOI

10.1016/j.celrep.2016.04.056

PubMed

27184840

Mer information

Senast uppdaterat

2018-09-06