Bioinformatics Analyses Identify the Therapeutic Potential of ST8SIA6 for Colon Cancer.

Chou-Yuan Ko,Hsin-Pao Chen,Tian-Huei Chu,Shiow-Jyu Tzou,Tung-Yuan Chen,Chuan-Fa Chang,Chung-Hsien Lin,Chen-Lin Chang,Shih-Chung Huang,Ching-Cheng Hsu,Yung-Kuo Lee,Pei-Chun Shih,Chia-Chen Lin

doi:10.3390/jpm12030401

Abstract

Sialylation of glycoproteins is modified by distinct sialyltransferases such as ST3Gal, ST6Gal, ST6GalNAc, or ST8SIA with α2,3-, α2,6-, or α2,8-linkages. Alteration of these sialyltransferases causing aberrant sialylation is associated with the progression of colon cancer. However, among the ST8- sialyltransferases, the role of ST8SIA6 in colon cancer remains poorly understood. In this study, we explored the involvement of ST8SIA6 in colon cancer using multiple gene databases. The relationship between ST8SIA6 expression and tumor stages/grades was investigated by UALCAN analysis, and Kaplan–Meier Plotter analysis was used to analyze the expression of ST8SIA6 on the survival outcome of colon cancer patients. Moreover, the biological functions of ST8SIA6 in colon cancer were explored using LinkedOmics and cancer cell metabolism gene DB. Finally, TIMER and TISMO analyses were used to delineate ST8SIA6 levels in tumor immunity and immunotherapy responses, respectively. ST8SIA6 downregulation was associated with an advanced stage and poorly differentiated grade; however, ST8SIA6 expression did not affect the survival outcomes in patients with colon cancer. Gene ontology analysis suggested that ST8SIA6 participates in cell surface adhesion, angiogenesis, and membrane vesicle trafficking. In addition, ST8SIA6 levels affected immunocyte infiltration and immunotherapy responses in colon cancer. Collectively, these results suggest that ST8SIA6 may serve as a novel therapeutic target towards personalized medicine for colon cancer.

Highlights

Colon cancer is the most common gastrointestinal malignancy
Disialic, oligosialic, and polysialic acids can be obtained by the addition of sialic acids via α2,8-linkage [11]. α2,8-linkage sialylation is catalyzed by six membranes of the α2,8 sialyltransferases (ST8SIA) family, which has been correlated with clinical outcomes [12]
To investigate the role of ST8SIA6 in colon cancer patients, we evaluated the RNA transcription levels of ST8SIA6 in multiple colon cancer studies from The Cancer Genome Atlas (TCGA)

Summary

Introduction

Colon cancer is the most common gastrointestinal malignancy. Several studies have shown that protein or lipid sialylation plays a crucial role in post-translational modifications during malignant tumor progression [3,4]. Sialyl Lewis x, sialyl Lewis a, sialyl Tn, and polysialic acid are well-studied and common carbohydrate tumor markers for the diagnosis, prognosis, and prediction of cancer [6–10]. Disialic acid on glycoproteins in mammals is associated with ST8SIA3 and ST8SIA6 in the human brain and other tissues [15–20]. According to Takashima et al and Teintenier-Lelievre et al studies have revealed mouse or human ST8SIA6 generates disialic acid in O-glycosylproteins. ST8SIA6 generates disialic acids that have been found in the α2,3-sialylated core 1 structure (Neu5Acα2,8Neu5Acα2,3Galβ1,34GalNAc-O-Ser) [18,21] and is important for binding to human Siglec-7 and murine Siglec-E. The interaction between Siglec-7 and surface glycoproteins or glycolipids with disialylation has been associated with human disease progression [22–24]. ST8SIA6 and Siglec-E expression was involved in tumor progression and diabetes by altering macrophage polarization and inflammation status [25,26]

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