Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

Abstract

Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

Epigenetic regulation of glycosylation and the impact on chemo-resistance in breast and ovarian cancer

“…For example, Ashkani et al, analyzed the differential expression of 210 glycosylation related genes from 6 different cancer types including breast and ovarian cancer. 49 Using specific software and statistical analyses they were able to identify each cancer type with a greater that 95% success rate using all 210 genes. 49 Ashkani et al, also successfully subtyped HER2-enriched and basal-like breast cancer from luminal types.…”

“…49 Using specific software and statistical analyses they were able to identify each cancer type with a greater that 95% success rate using all 210 genes. 49 Ashkani et al, also successfully subtyped HER2-enriched and basal-like breast cancer from luminal types. 49 Similar studies have been conducted by Potapenko et al, specifically looking at glycogene expression in breast cancer.…”

“…49 Ashkani et al, also successfully subtyped HER2-enriched and basal-like breast cancer from luminal types. 49 Similar studies have been conducted by Potapenko et al, specifically looking at glycogene expression in breast cancer. They assessed a panel of 419 glycogenes and successfully correlated them with diagnosis, progression, and survival.…”

O-linked mucin-type glycosylation regulates the transcriptional programme downstream of EGFR in breast cancer

“…Changes in glycosylation are very common in cancer and although increased sialylation is a common event, different tumour types can show different glycosylation patterns. Indeed different cancers can be clustered according to the expression of glycosyltransferases (32). The two O-linked glyco-phenotypes investigated here represent core 1 and sialylated core 1-based glycans (T47D), and core 2-based glycans (T47D-C2GnT1).…”

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8+ T cell apoptosis

“…While these new therapeutic approaches lower the Sia expression of tumors, the effect of complete tumor desialylation on the anti‐tumor immune response has never been investigated. Moreover, glycosylation patterns differ substantially between and within tumor types, urging the need to increase our understanding on how tumor‐associated glycan structures influence the immune system in tumors of different origins.…”