Tumor-dependent Effects of Proteoglycans and Various Glycosaminoglycan Synthesizing Enzymes and Sulfotransferases on Patients’ Outcome-Reference-Cited by-同舟云学术

Tumor-dependent Effects of Proteoglycans and Various Glycosaminoglycan Synthesizing Enzymes and Sulfotransferases on Patients’ Outcome

Published:2019-02-14 Issue:3 Volume:19 Page:210-221
ISSN:1568-0096
Container-title:Current Cancer Drug Targets
language:en
Short-container-title:CCDT

Author:

Subbarayan Karthikeyan¹,Seliger Barbara¹

Affiliation:

1. Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, 06112 Halle/ Saale, Germany

Abstract

Background: The small leucine-rich proteoglycans (SLRPs) biglycan (BGN) and decorin (DCN) linked with sulfated glycosaminoglycan (GAG) chains exhibit oncogenic or tumor suppressive potentials depending on the cellular context and association with GAGs. Objective: We hypothesized that structural alterations and expression levels of BGN, DCN and their associated chondroitin sulfate (CS) polymerizing enzymes, dermatan sulfate (DS) epimerases and various sulfatases might be correlated with the tumor (sub)type and patients’ survival. Methods: We acquired breast cancer (BC) and glioma patients’ datasets from cBioPortal and R2 Genomics. Structural alterations and the expression pattern of CS polymerizing enzymes, DS epimerases and carbohydrate sulfotransferases (CHST) were compared to that of BGN and DCN and correlated to their clinical relevance. Results: In BC, no mutations, but amplifications (0.2 – 2.1 %) and deletions (0.05 – 0.4 %) were found in BGN, DCN and CS/DS enzymes. In contrast, missense and/or truncated mutations (0.1 – 0.5 %), but a reduced amplification rate (0 – 1.5 %) were found in glioma. When compared to BC, the structural abnormalities caused altered mRNA expression levels of BGN, DCN, GAG synthesizing enzymes and CHST. Mutations in SLPRs, CHSY1, CHST4 and CHSY3 were correlated with a poor prognosis in glioma, while lack of mutations and copy number variations in the SLRPs, CHSY3, CHST15 and DSE displayed an increased survival in BC. Conclusion: A distinct association of BGN and DCN with CHST, CS polymerizing enzymes and DS epimerases was found in BC and glioma. Thus, a unique pattern of structural alterations and expression, which has clinical relevance, was found for PGs and GAG synthesizing enzymes and CHST in BC and glioma, which might help to identify high-risk patients and to develop personalized therapeutics.

Funder

Sander Stiftung

Publisher

Bentham Science Publishers Ltd.

Subject

Cancer Research,Drug Discovery,Pharmacology,Oncology

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