Comprehensive Transcriptomic Analysis Identifies ST8SIA1 as a Survival-Related Sialyltransferase Gene in Breast Cancer.

Jung-Yu Kan,Ming-Feng Hou,Wen-Chun Hung,Sin-Hua Moi,Chih-Po Chiang,Shen-Liang Shih,Fang-Ming Chen,Jun-Ping Shiau,Chung-Liang Li

doi:10.3390/genes11121436

Abstract

Hypersialylation caused by the overexpression of sialyltransferases (STs) is a common feature in cancer that is associated with several characteristics of tumorigenesis. Thus, identifying cancer-associated STs is critical for cancer therapy. However, ST screening has been frequently conducted in cell line models. In this study, we conducted a comprehensive analysis of STs in the clinical database and identified the STs related with the survival of breast cancer patients. RNA sequencing (RNA-Seq) data of 496 patients were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA). Of the eight mapped STs, ST3GAL5, and ST8SIA1 met the acceptable area under the curve (AUC) criteria for overall survival (OS). Using Kaplan–Meier methods, we determined that high expression of ST8SIA1 was associated with poor 10-year OS in all patients, triple-negative breast cancer (TNBC), and non-TNBC patients, and poor disease-free survival (DFS) rates particularly in TNBC. ST8SIA1 also had superior AUC values in terms of OS/DFS. High ST8SIA1 levels showed a higher risk for poor OS in different groups of patients and a higher risk for poor DFS particularly in TNBC. In summary, we conducted a comprehensive analysis of STs from the clinical database and identified ST8SIA1 as a crucial survival-related ST, which might be a potential therapeutic target for breast cancer and TNBC patients.

Highlights

Glycosylation is the main post-translational modification (PTM) in which glycans are conjugated to a protein at asparagine (N-linked) or serine/threonine (O-linked) residue, contributing to proteinGenes 2020, 11, 1436; doi:10.3390/genes11121436 www.mdpi.com/journal/genesGenes 2020, 11, 1436 functions such as cell-to-cell interaction, recognition, adhesion, and migration
The process of sialic acid incorporation into glycoconjugates on the cell surface is known as sialylation, and it is catalyzed by sialyltransferases (STs). 20 STs have been categorized into four groups: ST3Gal1-5, ST6Gal1-2, ST6GalNAc1-6, and ST8SIA1-6
496 samples were collected from TCGA-BRCA of the Genomic Data Commons (GDC) data portal. These breast cancer samples were further divided into the triple-negative breast cancer (TNBC, n = 110) and non-TNBC (n = 386) groups

Summary

Introduction

Glycosylation is the main post-translational modification (PTM) in which glycans are conjugated to a protein at asparagine (N-linked) or serine/threonine (O-linked) residue, contributing to proteinGenes 2020, 11, 1436; doi:10.3390/genes11121436 www.mdpi.com/journal/genesGenes 2020, 11, 1436 functions such as cell-to-cell interaction, recognition, adhesion, and migration. Glycosylation is the main post-translational modification (PTM) in which glycans are conjugated to a protein at asparagine (N-linked) or serine/threonine (O-linked) residue, contributing to protein. Aberrant glycosylation is a dominant feature of all human cancers that influences tumor proliferation, invasion, and metastasis. Hypersialylation is the most widely occurring cancer-associated glycosylation [1]. Sialic acid is a family of nine-carbon backbone glycans attached to the terminal position of glycoprotein/glycolipid on the cell surface. The process of sialic acid incorporation into glycoconjugates on the cell surface is known as sialylation, and it is catalyzed by sialyltransferases (STs). 20 STs have been categorized into four groups: ST3Gal, ST6Gal, ST6GalNAc1-6, and ST8SIA1-6. The four groups of STs are categorized according to (1) the linkage of carbon connecting the second carbon (C2)

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