Clinical Pathology, National Cancer Institute, Cairo University, Giza, Egypt.
Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
Hematology. 2021 Dec;26(1):758-768. doi: 10.1080/16078454.2021.1978763.
Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.
The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- cancer stem cells (CSCs) were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis.
There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, ], and CSCs CD34CD38 [1 (0.03-18.6) versus 0.3 (0.01-1.1), expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, area under curve (AUC) of MMP-2 were (80.3%, 53.3% and 0.568, = 0.404), and of MMP-9 were (53.9%, 40% and 0.660, = 0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, , and that of CD34CD38 CSCs were (78.9%, 73.3% and 0.855, . Increased TIMP-1 expression associated with the high-risk disease ). CD34CD38 CSCs and MMP-2 overexpression associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 ( ). TIMP-1 overexpression is associated with shorter DFS and OS rates ( and ). Multivariate logistic regression analysis showed that both TIMP-1 [ ], and CD34CD38 CSCs [ ] could be potential independent diagnostic factors for pediatric ALL.
TIMP-1 and CD34CD38 CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.
基质金属蛋白酶（MMPs）在癌症的进展和转移中起着至关重要的作用，但它们在儿科急性淋巴细胞白血病（ALL）中的作用仍未被揭示。
使用流式细胞术分析了 76 例 ALL 儿童骨髓（BM）样本中组织金属蛋白酶抑制剂（TIMP-1）、MMP-2、MMP-9 和 CD34+CD38-癌症干细胞（CSCs）的诊断、预后和预测价值。
与对照组相比，ALL 患者的 TIMP-1[1.52（0.41-10）与 0.91（0.6-1.12）；分别， ]和 CSCs CD34CD38[1（0.03-18.6）与 0.3（0.01-1.1）；分别，表达增加。而两组间 MMP-2 和 MMP-9 的表达无显著性差异。MMP-2 的灵敏度、特异性、曲线下面积（AUC）分别为（80.3%、53.3%和 0.568，=0.404），MMP-9 分别为（53.9%、40%和 0.660，=0.053）。而 TIMP-1 的灵敏度、特异性、AUC 分别为（78.9%、100%和 0.892， ），CD34CD38 CSCs 分别为（78.9%、73.3%和 0.855， ）。TIMP-1 表达增加与高危疾病相关。CD34CD38 CSCs 和 MMP-2 过表达与第 15 天的 MRD、诊断时和第 15 天的 BM 原始细胞计数增加相关（ ）。TIMP-1 过表达与较短的 DFS 和 OS 率相关（ 和 ）。多变量逻辑回归分析表明，TIMP-1 [ ]和 CD34CD38 CSCs [ ]均为儿科 ALL 的潜在独立诊断因素。
TIMP-1 和 CD34CD38 CSCs 可能是儿科 ALL 的有用诊断标志物。此外，TIMP-1 是预测患者不良预后的有前途的预后标志物。
