Plasma glycosaminoglycan scores in early stage renal cell carcinoma

Background: Previous studies have found an outstanding role in the regulation of metabolism of clear cell renal cell carcinoma (ccRCC; Gatto et al., 2014; Creighton et al., 2013). We discovered that glycosaminoglycan (GAG) biosynthesis was prominently regulated in ccRCC, and measurements of circulating GAGs could be condensed into scores that distinguished metastatic ccRCC with accuracy ranging 92.7% to 100% (Gatto et al., 2016). However, it is still unknown if GAG scores could detect cancer at earlier stages and across other histologies. Methods and Results: We measured plasma GAGs in pre-operative samples from a retrospective consecutive series of 218 patients with a radiographic finding of renal mass. A control group was formed with 19 healthy volunteers and 25 historical healthy samples. In clustering analyses, plasma GAGs distinguished the 179 RCC samples as a separate group in an unbiased fashion. The previous GAG score was updated and achieved an area-under-the-curve (AUC) equal to 0.994 (95% CI: 0.985 - 1) in the validation set with a sensitivity of 95.7%. The GAG score was not significantly associated with age or gender nor with any histopathologic features. Conclusions: Plasma GAG scores are specifically altered in RCC patients and can detect the disease irrespective of stage and histology with elevated accuracy.