Hallmarks of glycogene expression and glycosylation pathways in squamous and adenocarcinoma cervical cancer

Abstract

Background Dysregulation of glycogene expression in cancer can lead to aberrant glycan expression, which can promote tumorigenesis. Cervical cancer (CC) displays an increased expression of glycogenes involved in sialylation and sialylated glycans. Here, we show a comprehensive analysis of glycogene expression in CC to identify glycogene expression signatures and the possible glycosylation pathways altered. Methods First, we performed a microarray expression assay to compare glycogene expression changes between normal and cervical cancer tissues. Second, we used 401 glycogenes to analyze glycogene expression in adenocarcinoma and squamous carcinoma from RNA-seq data at the cBioPortal for Cancer Genomics. Results The analysis of the microarray expression assay indicated that CC displayed an increase in glycogenes related to GPI-anchored biosynthesis and a decrease in genes associated with chondroitin and dermatan sulfate with respect to normal tissue. Also, the glycogene analysis of CC samples by the RNA-seq showed that the glycogenes involved in the chondroitin and dermatan sulfate pathway were downregulated. Interestingly the adenocarcinoma tumors displayed a unique glycogene expression signature compared to squamous cancer that shows heterogeneous glycogene expression divided into six types. Squamous carcinoma type 5 (SCC-5) showed increased expression of genes implicated in keratan and heparan sulfate synthesis, glycosaminoglycan degradation, ganglio, and globo glycosphingolipid synthesis was related to poorly differentiated tumors and poor survival. Squamous carcinoma type 6 (SCC-6) displayed an increased expression of genes involved in chondroitin/dermatan sulfate synthesis and lacto and neolacto glycosphingolipid synthesis and was associated with nonkeratinizing squamous cancer and good survival. In summary, our study showed that CC tumors are not a uniform entity, and their glycome signatures could be related to different clinicopathological characteristics.

Prediction of the immunological and prognostic value of five signatures related to fatty acid metabolism in patients with cervical cancer

“…Research has pointed out that one of the key mechanisms of signal transduction in CC cells is the glycosylation of proteins (38). As a glycoprotein on the cell surface, N-Glycon directly affects cell signal transduction and is the diagnostic target of malignant transformation in the early stage of CC (39)(40)(41). O-glycan can be used as a biological marker of proliferation, senescence and metastasis of CC cells by B A FIGURE 11 Biological pathway for potential regulation of FAMRGs prognosis-related model (A) Heat map in which GSVA analysis of TCGA dataset pathway showed significant enrichment scores of related pathways in high and low risk groups, and (B) Heat map of correlation analysis of pathways with significant differences in TCGA data sets and RiskScores (*p<0.05,**p<0.01,***p<0.001).…”

“…Research has pointed out that one of the key mechanisms of signal transduction in CC cells is the glycosylation of proteins ( 38 ). As a glycoprotein on the cell surface, N-Glycon directly affects cell signal transduction and is the diagnostic target of malignant transformation in the early stage of CC ( 39 – 41 ). O-glycan can be used as a biological marker of proliferation, senescence and metastasis of CC cells by regulating immune response and controlling cell metabolism ( 42 , 43 ).…”

Multi-omics analysis of renal clear cell carcinoma progression

“…Gene expression of BCR was also upregulated in KIRP, a renal cancer closely related to RCC [30]. B3GALT1 is involved in the biosynthesis of the carbohydrate moieties of glycolipids and glycoproteins, and has been found to be involved in cervical adenosquamous carcinoma [31]. SPTSSB (serine palmitoyltransferase small subunit B) downregulation has been found to be detrimental to RCC patients [32].…”

Advances in the Immunomodulatory Properties of Glycoantigens in Cancer

“…Fundamental changes in the glycosylation patterns of cell surface and secreted glycoproteins occur during malignant transformation and cancer progression [1,3]. Changes in glycosylation induce the appearance of unmasked glycan antigens in the surface of tumour cells, known as tumour-associated carbohydrate antigens (TACAs) [3][4][5][6]. There is a vast amount of documented evidence that changes in glycosylation are a hallmark of cancer and their role in tumour development has been extensively studied [3,6].…”