Open AccessTissue glycomics distinguish tumour sites in women with advanced serous adenocarcinoma
Author(s) -
Anugraham Merrina,
Jacob Francis,
EverestDass Arun V.,
Schoetzau Andreas,
Nixdorf Sheri,
Hacker Neville F.,
Fink Daniel,
HeinzelmannSchwarz Viola,
Packer Nicolle H.
Publication year - 2017
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12134
Subject(s) - glycomics , serous fluid , glycan , ovarian cancer , cancer research , glycome , transcriptome , chemistry , biology , cancer , pathology , oncology , microbiology and biotechnology , gene , medicine , gene expression , biochemistry , glycoprotein
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 Lacdi NA c‐type (Gal NA cβ1‐4Glc NA c) motifs that were unique to the serous ovarian cancers and that correlated with elevated gene expression of B4 GALNT 3 and B4 GALNT 4 in patients with serous cancer. Statistical evaluation of the discriminatory glycans also revealed 13 N ‐ and 3 O ‐glycans ( P < 0.05) that significantly discriminated tumour‐sampling sites, with Lacdi NA c‐type N ‐glycans ( m / z 1205.0 2− and m / z 1059.4 2− ) being associated with ovarian‐derived cancer tissue and bisecting Glc NA c‐type ( m / z 994.9 2− ) and branched N ‐glycans ( m / z 1294.0 2− and m / z 1148.4 2− ) upregulated at the metastatic sites. Hence, we demonstrate for the first time that OC and PC display distinct molecular signatures at both their glycomic and transcriptomic levels. These signatures may have potential utility for the development of accurate diagnosis and personalized treatments.