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.
Highlights
The term cancer has come to describe complex malignant diseases that may not share the same causative agents, etiology or molecular profiles[5]
The underlying rationale for differential GT gene expression levels in six cancers is better understood through an understanding of the roles that the translated enzymes play in the reprogramming of the integrated intercellular circuitry and the sub circuits supporting tumour cell-biological properties
The combined effect of differential expression leading to cancer segregation and highly ranked importance of GT genes in cancer identification emphasizes that the biochemical pathways underlying key phenotypes across cancers differ significantly
Summary
The term cancer has come to describe complex malignant diseases that may not share the same causative agents, etiology or molecular profiles[5]. It is accepted that individual enzymes responsible for alterations in glycan structures could be biomarkers[6], a comparison of the collective enzymatic actions between cancers leading to type or subtype specific glycosylation profile definitions have not been considered. We found evidence that the changes of glycan structures are strongly implicated as signatures in malignant tumour typing and possibly subtyping. This PTM orchestrated by the regulation of GT genes and the subsequent biochemical action of glycosyltransferases engineers the restructuring of glycans that in turn play key roles in the progression toward malignancy reliant on tumorigenesis[7,8,9,10,11]. Cancer types (breast invasive carcinoma; BRCA, ovarian serous cystadenocarcinoma; OV, glioblastoma multiforme; GBM, kidney renal clear cell carcinoma; KIRC, colon adenocarcinoma; COAD and lung squamous cell carcinoma; LUSC)
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