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Protein N-glycosylation is one of the most important post-translational modifications and is involved in many biological processes, with aberrant changes in protein N-glycosylation patterns being closely associated with several diseases, including the progression and spreading of tumours. In light of this, identifying these aberrant protein glycoforms in tumours could be useful for understanding the molecular mechanism of this multifactorial disease, developing specific biomarkers and finding novel therapeutic targets. We investigated the urinary N-glycoproteome of clear cell renal cell carcinoma (ccRCC) patients at different stages (n = 15 at pT1 and n = 15 at pT3), and of non-ccRCC subjects (n = 15), using an N-glyco-FASP-based method. Using label-free nLC-ESI MS/MS, we identified and quantified several N-glycoproteins with altered expression and abnormal changes affecting the occupancy of the glycosylation site in the urine of RCC patients compared to control. In particular, nine of them had a specific trend that was directly related to the stage progression: CD97, COCH and P3IP1 were up-expressed whilst APOB, FINC, CERU, CFAH, HPT and PLTP were down-expressed in ccRCC patients. Overall, these results expand our knowledge related to the role of this post-translational modification in ccRCC and translation of this information into pre-clinical studies could have a significant impact on the discovery of novel biomarkers and therapeutic target in kidney cancer.

Urothelium, a specialized epithelium, covers the urinary tract and act not only as a barrier separating its light from the surrounding tissues, but fulfills an important role in maintaining the homeostasis of the urothelial tract and well-being of the whole organism. Proper function of urothelium is dependent on the precise assemble of highly specialized glycoproteins called uroplakins, the end products and differentiation markers of the urothelial cells. Glycosylation changes in uroplakins correlate with and might reflect progressive stages of pathological conditions of the urothelium such as cancer, urinary tract infections, interstitial cystitis and others. In this review we focus on sugar components of uroplakins, their emerging role in urothelial biology and disease implications. The advances in our understanding of uroplakins changes in glycan moieties composition, structure, assembly and expression of their glycovariants could potentially lead to the development of targeted therapies and discoveries of novel urine and plasma markers for the benefit of patients with urinary tract diseases.