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.
Highlights
Acute myeloid leukemia (AML) is a group of malignant myelopoietic stem/progenitor cell diseases, characterized by abnormal proliferation of primitive and immature myeloid cells in bone marrow and peripheral blood[1,2]
As shown in the results of RT-qPCR, the expression of Heparan sulfate proteoglycan 2 (HSPG2) was significantly upregulated in AML patients (Fig. 2a, P < 0.001), and human myeloid leukemia cell lines (SKM1 cells and K562 cells) (Fig. 2c, P < 0.001), but not in human T cell acute lymphoblastic leukemia cell line (Jurkat cells) (Fig. 2c, P > 0.05)
HSPG2 in AML patients compared with healthy controls and found the area under the ROC curve (AUC) value to be 0.903 in whole-cohort AML (95% confidence interval (CI): 0.842–0.965, P < 0.001; Fig. 3a) with a sensitivity of 88.0% and a specificity of 74.1%, which indicated that HSPG2 could be a potential biomarker for distinguishing AML patients from healthy controls
Summary
Acute myeloid leukemia (AML) is a group of malignant myelopoietic stem/progenitor cell diseases, characterized by abnormal proliferation of primitive and immature myeloid cells in bone marrow and peripheral blood[1,2]. Official journal of the Cell Death Differentiation Association. (CAPB) locus that hosts a series of oncogenes for prostate cancer and the brain tumor[10]. Previous studies have showed that high expression of HSPG2 might be an indicator of prostate cancer grade, invasion potential and distant metastasis[10,12]. An in vitro study found that HSPG2 is actively synthesized by bone marrow derived cells and the abnormal expression of HSPG2 might play a vital role in hematopoietic cell differentiation[15]. The role of HSPG2 remains unknown in AML
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