Clinical Pathology Department, Tanta University, Tanta 31527, Egypt.
Internal Medicine Department, Tanta University, Tanta 31527, Egypt.
Genes (Basel). 2022 May 26;13(6):948. doi: 10.3390/genes13060948.
Introduction: The prognosis of chronic myeloid leukemia (CML) patients has been dramatically improved with the introduction of imatinib (IM), the first tyrosine kinase inhibitor (TKI). TKI resistance is a serious problem in IM-based therapy. The human S-phase kinase-associated protein 2 (SKP2) gene may play an essential role in the genesis and progression of CML. Aim of the study: We try to explore the diagnostic/prognostic impact of SKP2 gene expression to predict treatment response in first-line IM-treated CML patients at an early response stage. Patients and methods: The gene expression and protein levels of SKP2 were determined using quantitative RT-PCR and ELISA in 100 newly diagnosed CML patients and 100 healthy subjects. Results: SKP2 gene expression and SKP2 protein levels were significantly upregulated in CML patients compared to the control group. The receiver operating characteristic (ROC) analysis for the SKP2 gene expression level, which that differentiated the CML patients from the healthy subjects, yielded a sensitivity of 86.0% and a specificity of 82.0%, with an area under the curve (AUC) of 0.958 (p < 0.001). The ROC analysis for the SKP2 gene expression level, which differentiated optimally from the warning/failure responses, yielded a sensitivity of 70.59% and a specificity of 71.21%, with an AUC of 0.815 (p < 0.001). Conclusion: The SKP2 gene could be an additional diagnostic and an independent prognostic marker for predicting treatment responses in first-line IM-treated CML patients at an early time point (3 months).
随着伊马替尼(IM)的引入,即第一种酪氨酸激酶抑制剂(TKI),慢性髓性白血病(CML)患者的预后得到了显著改善。TKI 耐药是 IM 为基础治疗中的一个严重问题。人类 S 期激酶相关蛋白 2(SKP2)基因可能在 CML 的发生和进展中起重要作用。
我们试图探讨 SKP2 基因表达对预测一线 IM 治疗的 CML 患者早期反应阶段治疗反应的诊断/预后影响。
使用定量 RT-PCR 和 ELISA 测定 100 例新诊断的 CML 患者和 100 例健康对照者的 SKP2 基因表达和 SKP2 蛋白水平。
与对照组相比,CML 患者的 SKP2 基因表达和 SKP2 蛋白水平显著上调。SKP2 基因表达水平区分 CML 患者和健康对照者的 ROC 分析,其敏感性为 86.0%,特异性为 82.0%,曲线下面积(AUC)为 0.958(p<0.001)。SKP2 基因表达水平最佳区分警告/失败反应的 ROC 分析,其敏感性为 70.59%,特异性为 71.21%,AUC 为 0.815(p<0.001)。
SKP2 基因可作为一线 IM 治疗的 CML 患者早期(3 个月)预测治疗反应的额外诊断和独立预后标志物。