HSPG2 overexpression independently predicts poor survival in patients with acute myeloid leukemia

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Abstract

Heparan sulfate proteoglycan 2 (HSPG2), also known as perlecan, is a large multi-domain extracellular matrix proteoglycan, which contributes to the invasion, metastasis and angiogenesis of solid tumor. However, very little is known about the effect of HSPG2 on acute myeloid leukemia (AML). This study aims to investigate the prognostic value of the HSPG2 gene in terms of overall survival and leukemia-free survival in patients with AML. Bone marrow mononuclear cells (BMMCs) from 4 AML patients and 3 healthy controls were processed for RNA-Sequencing (RNA-seq). The mRNA expression level of HSPG2 in BMMCs and CD34 ⁺ hematopoietic stem/progenitor cells (HSPC) obtained from enrolled participants and human leukemic cell lines was detected by RT-qPCR. Then the correlations between the expression of HSPG2 and a variety of important clinical parameters, such as median white blood cell (WBC) count and bone marrow (BM) blasts, were further analyzed. The expression level of HSPG2 was significantly upregulated in AML patients at the time of diagnosis, downregulated after complete remission and then elevated again at relapse. Moreover, HSPG2 expression was associated with median WBC count ( P < 0.001), median hemoglobin ( P = 0.02), median platelet count ( P = 0.001), and BM blasts ( P < 0.001) in AML patients. Patients with high HSPG2 expression had both worse overall survival (OS) ( P = 0.001) and poorer leukemia-free survival (LFS) ( P = 0.047). In the multivariate analysis model, HSPG2 was identified as an independent prognostic biomarker of AML. Taken together, these results indicate that HSPG2 overexpression was associated with poor prognosis in AML patients, and may be a prognostic biomarker and therapeutic target of AML.

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Author and article information

Contributors

Li Wang: liwangls@yahoo.com

Journal

Journal ID (nlm-ta): Cell Death Dis

Journal ID (iso-abbrev): Cell Death Dis

Title: Cell Death & Disease

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2041-4889

Publication date (Electronic): 30 June 2020

Publication date PMC-release: 30 June 2020

Publication date Collection: June 2020

Volume: 11

Issue: 6

Electronic Location Identifier: 492

Affiliations

[1 ]GRID grid.452206.7, Department of Hematology, , The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, China

[2 ]GRID grid.452206.7, The Center for Clinical Molecular Medical detection, , The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, China

[3 ]Center for the Study of Hematological Malignancies, Karaiskakio Foundation, 2032 Nicosia, Cyprus

Article

Publisher ID: 2694

DOI: 10.1038/s41419-020-2694-7

PMC ID: 7327006

PubMed ID: 32606327

SO-VID: c35c3b01-3a48-4812-83c7-4b66da4cfba3

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 31 January 2020

Date revision received : 13 June 2020

Date accepted : 16 June 2020

Funding

Funded by: This work was supported by Natural Science Foundation Project of Chongqing (cstc2018jcyjAX0688), Chongqing Science and Health joint project (2018ZDXM001), and Chongqing Education Commission Foundation (KJ1702017).