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成人体急性髓系白血病中 FAK 及其部分效应物的血清水平:与预后因素和生存的相关性。

Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival.

机构信息

Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

Department of Internal Medicine, Clinical Hematology and Oncology Division, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

出版信息

Mol Cell Biochem. 2021 May;476(5):1949-1963. doi: 10.1007/s11010-020-04030-z. Epub 2021 Jan 28.

DOI:10.1007/s11010-020-04030-z
PMID:33507464
Abstract

Focal adhesion kinase (FAK), human myofibrillogenesis regulator-1 (MR-1), ephrin receptor type A4 (EphA4), proto-oncogene tyrosine kinase Src (Src), and protein kinase C (PKC) are important markers in proliferation, survival, and migration in some cancers. However, the significance of each is still unclear in different malignancies, including acute myeloid leukemia (AML). Therefore, this study was conducted to investigate their serum levels in Egyptian adult de novo AML patients (n = 70) against healthy volunteers (n = 20). We managed to study the correlation between each pair and to investigate their association with diagnosis, prognosis, and survival. Serum levels were analyzed using enzyme-linked immunosorbent assay (ELISA). We found that FAK, MR-1, Src, and PKC serum levels were significantly higher in AML patients compared to control (p < 0.0001), and this was associated with significantly lower EphA4 level (p < 0.0001). Interestingly, we also observed a significant negative correlation of FAK (p = 0.027), MR-1 (p = 0.003), Src (p = 0.038), and PKC (p = 0.03) with patients' overall survival (OS) while there was a positive significant correlation between EphA4 and OS (p = 0.007). In conclusion, this study suggests that FAK, MR-1, EphA4, Src, and PKC may be used as early diagnostic and prognostic markers with high sensitivity and specificity in AML patients and thus may be incorporated into the patients' early diagnostic and prognostic panels.

摘要

黏着斑激酶(FAK)、人类肌原纤维生成调节剂-1(MR-1)、表皮生长因子受体 A4(EphA4)、原癌基因酪氨酸激酶Src(Src)和蛋白激酶 C(PKC)是一些癌症中增殖、存活和迁移的重要标志物。然而,在不同的恶性肿瘤中,包括急性髓系白血病(AML),每种标志物的意义仍然不清楚。因此,本研究旨在调查埃及初诊 AML 成年患者(n=70)与健康志愿者(n=20)血清中这些标志物的水平。我们成功地研究了每对标志物之间的相关性,并探讨了它们与诊断、预后和生存的关系。使用酶联免疫吸附试验(ELISA)分析血清水平。我们发现,与对照组相比,AML 患者的 FAK、MR-1、Src 和 PKC 血清水平显著升高(p<0.0001),而 EphA4 水平显著降低(p<0.0001)。有趣的是,我们还观察到 FAK(p=0.027)、MR-1(p=0.003)、Src(p=0.038)和 PKC(p=0.03)与患者总生存(OS)呈显著负相关,而 EphA4 与 OS 呈显著正相关(p=0.007)。总之,本研究表明,FAK、MR-1、EphA4、Src 和 PKC 可作为 AML 患者早期诊断和预后的标志物,具有较高的灵敏度和特异性,可纳入患者的早期诊断和预后评估。

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