Comprehensive Transcriptomic Analysis Identifies As a Survival-Related Sialyltransferase Gene in Breast Cancer

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2020 Dec 2

PMID 33260650

Citations 6

Authors

Jung-Yu Kan

Sin-Hua Moi

Wen-Chun Hung

Ming-Feng Hou

Fang-Ming Chen

Shen-Liang Shih

Jun-Ping Shiau

Chung-Liang Li

Chih-Po Chiang

Affiliations

Soon will be listed here.

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, , and met the acceptable area under the curve (AUC) criteria for overall survival (OS). Using Kaplan-Meier methods, we determined that high expression of 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. also had superior AUC values in terms of OS/DFS. High 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 as a crucial survival-related ST, which might be a potential therapeutic target for breast cancer and TNBC patients.

Citing Articles

The biological role and immunotherapy of gangliosides and GD3 synthase in cancers.

Cao S, Hu X, Ren S, Wang Y, Shao Y, Wu K Front Cell Dev Biol. 2023; 11:1076862.

PMID: 36824365 PMC: 9941352. DOI: 10.3389/fcell.2023.1076862.

Sialyltransferases and Neuraminidases: Potential Targets for Cancer Treatment.

Nag S, Mandal A, Joshi A, Jain N, Srivastava R, Singh S Diseases. 2022; 10(4).

PMID: 36547200 PMC: 9777960. DOI: 10.3390/diseases10040114.

ST3GAL5-catalyzed gangliosides inhibit TGF-β-induced epithelial-mesenchymal transition via TβRI degradation.

Zhang J, van der Zon G, Ma J, Mei H, Cabukusta B, Agaser C EMBO J. 2022; 42(2):e110553.

PMID: 36504224 PMC: 9841337. DOI: 10.15252/embj.2021110553.

Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer.

Li C, Moi S, Lin H, Hou M, Chen F, Shih S Int J Mol Sci. 2022; 23(18).

PMID: 36142451 PMC: 9501051. DOI: 10.3390/ijms231810539.

The Distinct Roles of Sialyltransferases in Cancer Biology and Onco-Immunology.

Hugonnet M, Singh P, Haas Q, von Gunten S Front Immunol. 2022; 12:799861.

PMID: 34975914 PMC: 8718907. DOI: 10.3389/fimmu.2021.799861.

References

Li F, Ding J . Sialylation is involved in cell fate decision during development, reprogramming and cancer progression. Protein Cell. 2018; 10(8):550-565. PMC: 6626595. DOI: 10.1007/s13238-018-0597-5. View

Chang T, Chin Y, Nana A, Wang S, Liao Y, Chen Y . Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation. Horm Cancer. 2018; 9(6):420-432. PMC: 6223990. DOI: 10.1007/s12672-018-0341-x. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Ruckhaberle E, Karn T, Rody A, Hanker L, Gatje R, Metzler D . Gene expression of ceramide kinase, galactosyl ceramide synthase and ganglioside GD3 synthase is associated with prognosis in breast cancer. J Cancer Res Clin Oncol. 2009; 135(8):1005-13. DOI: 10.1007/s00432-008-0536-6. View

Wan H, Li Z, Wang H, Cai F, Wang L . ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/β-catenin and FAK/Akt/mTOR. Clin Transl Oncol. 2020; 23(4):902-910. DOI: 10.1007/s12094-020-02484-7. View

ASHWELL G, Morell A . The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol Relat Areas Mol Biol. 1974; 41(0):99-128. DOI: 10.1002/9780470122860.ch3. View

Murugaesu N, Iravani M, van Weverwijk A, Ivetic A, Johnson D, Antonopoulos A . An in vivo functional screen identifies ST6GalNAc2 sialyltransferase as a breast cancer metastasis suppressor. Cancer Discov. 2014; 4(3):304-17. DOI: 10.1158/2159-8290.CD-13-0287. View

Todeschini A, Hakomori S . Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim Biophys Acta. 2007; 1780(3):421-33. PMC: 2312458. DOI: 10.1016/j.bbagen.2007.10.008. View

Fuster M, Esko J . The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer. 2005; 5(7):526-42. DOI: 10.1038/nrc1649. View

10.

Ruckhaberle E, Rody A, Engels K, Gaetje R, von Minckwitz G, Schiffmann S . Microarray analysis of altered sphingolipid metabolism reveals prognostic significance of sphingosine kinase 1 in breast cancer. Breast Cancer Res Treat. 2007; 112(1):41-52. DOI: 10.1007/s10549-007-9836-9. View

11.

Schauer R . Achievements and challenges of sialic acid research. Glycoconj J. 2001; 17(7-9):485-99. PMC: 7087979. DOI: 10.1023/a:1011062223612. View

12.

Chiodelli P, Urbinati C, Paiardi G, Monti E, Rusnati M . Sialic acid as a target for the development of novel antiangiogenic strategies. Future Med Chem. 2018; 10(24):2835-2854. DOI: 10.4155/fmc-2018-0298. View

13.

Su M, Chang T, Chiang C, Chang H, Hou M, Li W . Inhibition of chemokine (C-C motif) receptor 7 sialylation suppresses CCL19-stimulated proliferation, invasion and anti-anoikis. PLoS One. 2014; 9(6):e98823. PMC: 4051673. DOI: 10.1371/journal.pone.0098823. View

14.

Shamon L, Pezzuto J, GRAVES J, Mehta R, Wangcharoentrakul S, Sangsuwan R . Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 1997; 112(1):113-7. DOI: 10.1016/S0304-3835(96)04554-5. View

15.

Groux-Degroote S, Rodriguez-Walker M, Dewald J, Daniotti J, Delannoy P . Gangliosides in Cancer Cell Signaling. Prog Mol Biol Transl Sci. 2018; 156:197-227. DOI: 10.1016/bs.pmbts.2017.10.003. View

16.

Nguyen K, Yan Y, Yuan B, Dasgupta A, Sun J, Mu H . ST8SIA1 Regulates Tumor Growth and Metastasis in TNBC by Activating the FAK-AKT-mTOR Signaling Pathway. Mol Cancer Ther. 2018; 17(12):2689-2701. PMC: 6279518. DOI: 10.1158/1535-7163.MCT-18-0399. View

17.

Chiang C, Wang C, Chang H, More S, Li W, Hung W . A novel sialyltransferase inhibitor AL10 suppresses invasion and metastasis of lung cancer cells by inhibiting integrin-mediated signaling. J Cell Physiol. 2010; 223(2):492-9. DOI: 10.1002/jcp.22068. View

18.

Seales E, Shaikh F, Woodard-Grice A, Aggarwal P, McBrayer A, Hennessy K . A protein kinase C/Ras/ERK signaling pathway activates myeloid fibronectin receptors by altering beta1 integrin sialylation. J Biol Chem. 2005; 280(45):37610-5. DOI: 10.1074/jbc.M508476200. View

19.

Zhou X, Yang G, Guan F . Biological Functions and Analytical Strategies of Sialic Acids in Tumor. Cells. 2020; 9(2). PMC: 7072699. DOI: 10.3390/cells9020273. View

20.

Szabo R, Skropeta D . Advancement of Sialyltransferase Inhibitors: Therapeutic Challenges and Opportunities. Med Res Rev. 2016; 37(2):219-270. DOI: 10.1002/med.21407. View