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Mol Oncol. 2015 Apr;9(4):861-76. doi: 10.1016/j.molonc.2014.12.013. Epub 2015 Jan 14.

Glycan-related gene expression signatures in breast cancer subtypes; relation to survival.

Author information

1
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Norway; K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
2
Department of Clinical Epidemiology and Molecular Biology (Epi-Gen), Akershus University Hospital, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
3
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Norway; K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Oncology, Oslo University Hospital Radiumhospitalet, Norway.
4
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Norway; K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway; Department of Clinical Epidemiology and Molecular Biology (Epi-Gen), Akershus University Hospital, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
5
Institute for Informatics, Faculty of Natural Sciences and Mathematics, University of Oslo, Norway.
6
Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Norway; K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Norway. Electronic address: vilde.drageset.haakensen@rr-research.no.

Abstract

Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their association to clinical parameters. Five expression datasets of 454 invasive breast carcinomas, 31 ductal carcinomas in situ (DCIS), and 79 non-malignant breast tissue samples were analysed. Results were validated in 1960 breast carcinomas. 419 genes encoding glycosylation-related proteins were selected. The DCIS samples appeared expression-wise similar to carcinomas, showing altered gene expression related to glycosaminoglycans (GAGs) and N-glycans when compared to non-malignant samples. In-situ lesions with different aggressiveness potentials demonstrated changes in glycosaminoglycan sulfation and adhesion proteins. Subtype-specific expression patterns revealed down-regulation of genes encoding glycan-binding proteins in the luminal A and B subtypes. Clustering basal-like samples using a consensus list of genes differentially expressed across discovery datasets produced two clusters with significantly differing prognosis in the validation dataset. Finally, our analyses suggest that glycolipids may play an important role in carcinogenesis of breast tumors - as demonstrated by association of B3GNT5 and UGCG genes to patient survival. In conclusion, most glycan-specific changes occur early in the carcinogenic process. We have identified glycan-related alterations specific to breast cancer subtypes including a prognostic signature for two basal-like subgroups. Future research in this area may potentially lead to markers for better prognostication and treatment stratification of breast cancer patients.

KEYWORDS:

Breast cancer; Carcinogenesis; Gene expression profiling; Glycosphingolipids; Glycosylation; Survival

PMID:
25655580
PMCID:
PMC5528768
DOI:
10.1016/j.molonc.2014.12.013
[Indexed for MEDLINE]
Free PMC Article

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