Serum N‐glycan analysis in breast cancer patients – Relation to tumour biology and clinical outcome

Abstract

Glycosylation and related processes play important roles in cancer development and progression, including metastasis. Several studies have shown that N-glycans have potential diagnostic value as cancer serum biomarkers. We have explored the significance of the abundance of particular serum N-glycan structures as important features of breast tumour biology by studying the serum glycome and tumour transcriptome (mRNA and miRNA) of 104 breast cancer patients. Integration of these types of molecular data allows us to study the relationship between serum glycans and transcripts representing functional pathways, such as metabolic pathways or DNA damage response. We identified tri antennary trigalactosylated trisialylated glycans in serum as being associated with lower levels of tumour transcripts involved in focal adhesion and integrin-mediated cell adhesion. These glycan structures were also linked to poor prognosis in patients with ER negative tumours. High abundance of simple monoantennary glycan structures were associated with increased survival, particularly in the basal-like subgroup. The presence of circulating tumour cells was found to be significantly associated with several serum glycome structures like bi and triantennary, di- and trigalactosylated, di- and trisialylated. The link between tumour miRNA expression levels and N-glycan production is also examined.

Serum N‐glycome alterations in breast cancer during multimodal treatment and follow‐up

“…Haakensen et al . () observed that this glycan is correlated with decreased mitochondrial fatty acid beta oxidation. Decrease in this glycan in cancer indicates an increase in cell energy production.…”

“…All glycans and derived glycan features were assigned in Saldova et al (2014). The major glycans in each peak, selected in Haakensen et al (2016), are summarized in Table 2.…”

“…, Table ). In previous studies, we have found that it strongly correlates with increased BMI and is associated with decreased integrin‐mediated cell adhesion and decreased adipocyte activity (Haakensen et al ., ). An increase in BMI reduces adipocyte activity and increases inflammation and the risk of cancer (van Kruijsdijk et al ., ).…”

Glycosylation and metastases

“…After separation by hydrophilic‐interaction chromatography (HILIC) or capillary electrophoresis, glycans are identified by mass spectrometry . Identification of individual oligosaccharides by their retention time in HILIC, enables very fast analysis of glycome, especially in biological fluids such as serum plasma, or urine . Profiling of both cell‐surface and intracellular glycans is more complicated and requires additional steps such as cell or tissue homogenization and fractionation .…”

“… underlined the necessity for a “multi‐omics” approach and data analysis in order to understand “the transition from healthy physiology to a disease state.” Haakensen et al. used this approach, and by studying the serum glycome and tumor transcriptome (mRNA and miRNA), they could demonstrate that the presence of circulating tumor cells is associated with certain glycome structures. Recent reviews present this approach, and its possible use for the optimization of different cancer therapies is widely discussed .…”