Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
The Center for Clinical Molecular Medical detection, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Cell Death Dis. 2020 Jun 30;11(6):492. doi: 10.1038/s41419-020-2694-7.
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.
硫酸乙酰肝素蛋白聚糖 2（HSPG2），也称为 perlecan，是一种大型多结构域细胞外基质蛋白聚糖，有助于实体瘤的侵袭、转移和血管生成。然而，对于 HSPG2 对急性髓系白血病（AML）的影响知之甚少。本研究旨在探讨 HSPG2 基因在 AML 患者总生存和无白血病生存方面的预后价值。对 4 例 AML 患者和 3 例健康对照者的骨髓单核细胞（BMMC）进行 RNA 测序（RNA-seq）。采用 RT-qPCR 检测纳入患者和人白血病细胞系中 BMMC 和 CD34 造血干/祖细胞（HSPC）中 HSPG2 的 mRNA 表达水平。然后进一步分析 HSPG2 表达与各种重要临床参数（如中位白细胞（WBC）计数和骨髓（BM）原始细胞）之间的相关性。AML 患者诊断时 HSPG2 表达水平显著上调，完全缓解后下调，复发时再次上调。此外，HSPG2 表达与 AML 患者的中位 WBC 计数（P<0.001）、中位血红蛋白（P=0.02）、中位血小板计数（P=0.001）和 BM 原始细胞（P<0.001）相关。HSPG2 高表达患者的总生存（OS）（P=0.001）和无白血病生存（LFS）（P=0.047）均较差。在多变量分析模型中，HSPG2 被确定为 AML 的独立预后生物标志物。综上所述，这些结果表明 HSPG2 过表达与 AML 患者的不良预后相关，可能是 AML 的预后生物标志物和治疗靶点。
