Urinary glycoproteomic profiling of non-muscle invasive and muscle invasive bladder carcinoma patients reveals distinct N-glycosylation pattern of CD44, MGAM, and GINM1

Gajanan Sathe, Irene A. George, Barnali Deb, Ankit P. Jain, Krishna Patel, Brusabhanu Nayak, Subhradip Karmakar, Amlesh Seth, Akhilesh Pandey, Prashant Kumar (Lead / Corresponding author)

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Abstract

Clinical management of bladder carcinomas (BC) remains a major challenge and demands comprehensive multi-omics analysis for better stratification of the disease. Identification of patients on risk requires identification of signatures predicting prognosis risk of the patients. Understanding the molecular alterations associated with the disease onset and progression could improve the routinely used diagnostic and therapy procedures. In this study, we investigated the aberrant changes in N-glycosylation pattern of proteins associated with tumorigenesis as well as disease progression in bladder cancer. We integrated and compared global N-glycoproteomic and proteomic profile of urine samples from bladder cancer patients at different clinicopathological stages (non-muscle invasive and muscle-invasive patients [n = 5 and 4 in each cohort]) with healthy subjects (n = 5) using SPEG method. We identified 635 N-glycopeptides corresponding to 381 proteins and 543 N-glycopeptides corresponding to 326 proteins in NMIBC and MIBC patients respectively. Moreover, we identified altered glycosylation in 41 NMIBC and 21 MIBC proteins without any significant change in protein abundance levels. In concordance with the previously published bladder cancer cell line N-glycoproteomic data, we also observed dysregulated glycosylation in ECM related proteins. Further, we identified distinct N-glycosylation pattern of CD44, MGAM, and GINM1 between NMIBC and MIBC patients, which may be associated with disease progression in bladder cancer. These aberrant protein glycosylation events would provide a novel approach for bladder carcinoma diagnosis and further define novel mechanisms of tumor initiation and progression.

Original languageEnglish
Pages (from-to)3244-3255
Number of pages12
JournalOncotarget
Volume11
Issue number34
DOIs
Publication statusPublished - 25 Aug 2020

Keywords

  • MIBC
  • N-linked glycoproteomics
  • NMIBC
  • Urine proteomics
  • Urothelial carcinoma

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