Behavior of blood plasma glycan features in bladder cancer

Shadi Ferdosi, Thai H. Ho, Erik P. Castle, Melissa L. Stanton, Chad Borges

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Despite systemic therapy and cystectomy, bladder cancer is characterized by a high recurrence rate. Serum glycomics represents a promising source of prognostic markers for monitoring patients. Our approach, which we refer to as “glycan node analysis”, constitutes the first example of molecularly “bottom-up” glycomics. It is based on a global glycan methylation analysis procedure that is applied to whole blood plasma/serum. The approach detects and quantifies partially methylated alditol acetates arising from unique glycan features such as α2–6 sialylation, β1–4 branching, and core fucosylation that have been pooled together from across all intact glycans within a sample into a single GC-MS chromatographic peak. We applied this method to 122 plasma samples from former and current bladder cancer patients (n = 72 former cancer patients with currently no evidence of disease (NED); n = 38 non-muscle invasive bladder cancer (NMIBC) patients; and n = 12 muscle invasive bladder cancer (MIBC) patients) along with plasma from 30 certifiably healthy living kidney donors. Markers for α2–6 sialylation, β1–4 branching, β1–6 branching, and outer-arm fucosylation were able to separate current and former (NED) cases from certifiably healthy controls (ROC curve c-statistics ~ 0.80); but NED, NMIBC, and MIBC were not distinguished from one another. Based on the unexpectedly high levels of these glycan nodes in the NED patients, we hypothesized that recurrence of this disease could be predicted by some of the elevated glycan features. Indeed, α2–6 sialylation and β1–6 branching were able to predict recurrence from the NED state using a Cox proportional hazards regression model adjusted for age, gender, and time from cancer. The levels of these two glycan features were correlated to C-reactive protein concentration, an inflammation marker and known prognostic indicator for bladder cancer, further strengthening the link between inflammation and abnormal plasma protein glycosylation.

Original languageEnglish (US)
Article numbere0201208
JournalPLoS One
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

blood plasma
Urinary Bladder Neoplasms
Polysaccharides
Blood
polysaccharides
Plasmas
branching
Glycomics
blood serum
Recurrence
Muscle
Muscle Neoplasms
inflammation
alditols
Inflammation
Sugar Alcohols
Glycosylation
Patient monitoring
muscles
neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Ferdosi, S., Ho, T. H., Castle, E. P., Stanton, M. L., & Borges, C. (2018). Behavior of blood plasma glycan features in bladder cancer. PLoS One, 13(7), [e0201208]. https://doi.org/10.1371/journal.pone.0201208

Behavior of blood plasma glycan features in bladder cancer. / Ferdosi, Shadi; Ho, Thai H.; Castle, Erik P.; Stanton, Melissa L.; Borges, Chad.

In: PLoS One, Vol. 13, No. 7, e0201208, 01.07.2018.

Research output: Contribution to journalArticle

Ferdosi, S, Ho, TH, Castle, EP, Stanton, ML & Borges, C 2018, 'Behavior of blood plasma glycan features in bladder cancer', PLoS One, vol. 13, no. 7, e0201208. https://doi.org/10.1371/journal.pone.0201208
Ferdosi, Shadi ; Ho, Thai H. ; Castle, Erik P. ; Stanton, Melissa L. ; Borges, Chad. / Behavior of blood plasma glycan features in bladder cancer. In: PLoS One. 2018 ; Vol. 13, No. 7.
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