背景:确定高危T细胞急性淋巴细胞白血病(T-ALL)患者对于个性化治疗至关重要,然而,缺乏稳健的生物标志物阻碍了预后评估.为了解决这个问题,我们的研究旨在筛选和验证其表达可作为T-ALL患者预后预测指标的基因,同时还研究了潜在的分子机制。
方法:通过整合来自三个独立公共数据集的数据来鉴定T-ALL患者和健康对照之间的差异表达基因(DEGs)。还进行了这些DEGs和蛋白质-蛋白质相互作用的功能注释。Further,我们在我们中心招募了一个T-ALL患者的前瞻性队列(n=20),对他们的骨髓样本进行RNA-seq分析。基于生存的单变量Cox分析用于鉴定与生存相关的基因表达,并依次应用了交叉算法。此外,我们使用治疗应用研究中的案例验证了已识别的基因,以产生有效的治疗数据库,绘制卡普兰-迈耶曲线进行二次验证。
结果:通过将生存相关基因与T-ALL中鉴定的DEGs整合,我们的分析揭示了六个T-ALL特异性基因,其表达水平与预后价值相关。值得注意的是,我们中心的外部队列和前瞻性队列均证实了SLC40A1和TES表达水平的独立预后价值.
结论:总之,我们的初步研究表明,TES和SLC40A1基因的表达水平有望作为预测T-ALL患者生存结局的潜在指标.
BACKGROUND: Identifying patients with high-risk T-cell acute lymphoblastic leukemia (T-ALL) is crucial for personalized therapy; however, the lack of robust biomarkers hinders prognosis assessment. To address this issue, our study aimed to screen and validate genes whose expression may serve as predictive indicators of outcomes in T-ALL patients while also investigating the underlying molecular mechanisms.
METHODS: Differentially expressed genes (DEGs) between T-ALL patients and healthy controls were identified by integrating data from three independent public datasets. Functional annotation of these DEGs and protein-protein interactions were also conducted. Further, we enrolled a prospective cohort of T-ALL patients (n = 20) at our center, conducting RNA-seq analysis on their bone marrow samples. Survival-based univariate Cox analysis was employed to identify gene expressions related to survival, and an intersection algorithm was sequentially applied. Furthermore, we validated the identified genes using cases from the Therapeutically Applicable Research to Generate Effective Treatments database, plotting Kaplan-Meier curves for secondary validation.
RESULTS: Through the integration of survival-related genes with DEGs identified in T-ALL, our analysis revealed six T-ALL-specific genes, the expression levels of which were linked to prognostic value. Notably, the independent prognostic value of SLC40A1 and TES expression levels was confirmed in both an external cohort and a prospective cohort at our center.
CONCLUSIONS: In summary, our preliminary study indicates that the expression levels of TES and SLC40A1 genes show promise as potential indicators for predicting survival outcomes in T-ALL patients.