In our quest to understand metabolic regulation in cancer using a global and unbiased systems biology approach, glycosaminoglycan (GAG) biosynthesis charted amongst the most prominently perturbed pathways across different cancers (Gatto et al., 2014) In renal cell carcinoma (RCC), the most common form of kidney cancer, we observed that virtually every step in the biosynthesis of chondroitin (CS) and heparan sulfate (HS) was deregulated at the transcript and protein level. We sought to explore whether this outstanding regulation translated into alterations of GAGs in kidney-proximal fluids – urine and plasma – in patients with RCC and thereby serve as disease biomarkers. In our first multicenter study at Veneto Institute of Oncology, Italy and Sahlgrenska University Hospital, Sweden, we obtained retrospective and prospective plasma and urine samples from 83 healthy and RCC patients with metastatic disease. We next measured the complete CS and HS profiles. These showed dramatic differences in metastatic RCC versus healthy, both in plasma and urine.
Glycosaminoglycan profiling as a novel pan-cancer minimally invasive systems biomarker / Gatto, Francesco; Blum, Kyle A.; Maruzzo, Marco; Nilsson, Helén; Nookaew, Intawat; Roma, Anna; Ghaanat, Mazyar; Maccari, Francesca; Galeotti, Fabio; Hsieh, James; Johansson, Martin E.; Consortium, Ucan; Volpi, Nicola; Basso, Umberto; Stierner, Ulrika; Lundstam, Sven; Ari Hakimi, A.; Nielsen., and Jens. - (2018). (Intervento presentato al convegno Proteoglycans in Homeostasis and Disease: Cracking the PG Code. Proteoglycans Gordon Research Conference. tenutosi a Andover, NH, US nel July 8 - 13, 2018).