Tissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma

In the era of precision medicine, the tailoring of cancer treatment is increasingly important as we transition from organ‐based diagnosis towards a more comprehensive and patient‐centric molecular diagnosis. This is particularly the case for high‐grade serous adenocarcinomas of the ovary and periton...

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Bibliographic Details
Published in:Molecular oncology 2017-11, Vol.11 (11), p.1595-1615
Main Authors: Anugraham, Merrina, Jacob, Francis, Everest‐Dass, Arun V., Schoetzau, Andreas, Nixdorf, Sheri, Hacker, Neville F., Fink, Daniel, Heinzelmann‐Schwarz, Viola, Packer, Nicolle H.
Format: Article
Language:English
Subjects:
Abdomen
Adenocarcinoma
Biomarkers
Cancer
Cell adhesion & migration
Cell Line, Tumor
Chromatography
Cystadenocarcinoma, Serous - genetics
Cystadenocarcinoma, Serous - pathology
Diagnosis
Female
Gastric cancer
Gene expression
Generalized linear models
glycans
Glycomics
Glycoproteins
Gynecology
Humans
Isomers
mass spectrometry
Medical prognosis
Medical research
Menopause
Metastases
Mortality
N-Acetylgalactosaminyltransferases - genetics
Obstetrics
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - pathology
peritoneal cancer
Peritoneal Neoplasms - genetics
Peritoneal Neoplasms - pathology
Peritoneum
Polysaccharides
Polysaccharides - analysis
Polysaccharides - genetics
porous graphitized carbon
Precision medicine
Statistical analysis
Studies
Survival analysis
Tandem Mass Spectrometry - methods
Transcriptome
Tumors
Women
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Summary:In the era of precision medicine, the tailoring of cancer treatment is increasingly important as we transition from organ‐based diagnosis towards a more comprehensive and patient‐centric molecular diagnosis. This is particularly the case for high‐grade serous adenocarcinomas of the ovary and peritoneum, which are commonly diagnosed at an advanced stage, and collectively treated and managed similarly. We characterized the N‐ and O‐glycome of serous ovarian (OC) and peritoneal cancer (PC) tissues using PGC‐LC‐ESI‐IT‐MS/MS profiling and validated the discriminatory glycans and their corresponding glyco‐gene expression levels using cell lines and transcriptomic data from 232 patients. Overall, the N‐ and O‐glycan repertoires of both cancer types were found to comprise mostly of α2,6‐sialylated glycan structures, with the majority of N‐glycans displaying the biantennary mono‐ and disialylation as well as bisecting‐type biantennary glycans. The MS profiling by PGC‐LC also revealed several glycan structural isomers that corresponded to LacdiNAc‐type (GalNAcβ1‐4GlcNAc) motifs that were unique to the serous ovarian cancers and that correlated with elevated gene expression of B4GALNT3 and B4GALNT4 in patients with serous cancer. Statistical evaluation of the discriminatory glycans also revealed 13 N‐ and 3 O‐glycans (P 
ISSN:1574-7891
1878-0261
DOI:10.1002/1878-0261.12134