铜死亡相关 lncRNA 特征可预测急性髓系白血病患者的预后。
Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia.
机构信息
Department of Traditional Chinese Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
出版信息
BMC Bioinformatics. 2023 Feb 3;24(1):37. doi: 10.1186/s12859-023-05148-9.
BACKGROUND
Long non-coding RNAs (lncRNAs) have been reported to have a crucial impact on the pathogenesis of acute myeloid leukemia (AML). Cuproptosis, a copper-triggered modality of mitochondrial cell death, might serve as a promising therapeutic target for cancer treatment and clinical outcome prediction. Nevertheless, the role of cuproptosis-related lncRNAs in AML is not fully understood.
METHODS
The RNA sequencing data and demographic characteristics of AML patients were downloaded from The Cancer Genome Atlas database. Pearson correlation analysis, the least absolute shrinkage and selection operator algorithm, and univariable and multivariable Cox regression analyses were applied to identify the cuproptosis-related lncRNA signature and determine its feasibility for AML prognosis prediction. The performance of the proposed signature was evaluated via Kaplan-Meier survival analysis, receiver operating characteristic curves, and principal component analysis. Functional analysis was implemented to uncover the potential prognostic mechanisms. Additionally, quantitative real-time PCR (qRT-PCR) was employed to validate the expression of the prognostic lncRNAs in AML samples.
RESULTS
A signature consisting of seven cuproptosis-related lncRNAs (namely NFE4, LINC00989, LINC02062, AC006460.2, AL353796.1, PSMB8-AS1, and AC000120.1) was proposed. Multivariable cox regression analysis revealed that the proposed signature was an independent prognostic factor for AML. Notably, the nomogram based on this signature showed excellent accuracy in predicting the 1-, 3-, and 5-year survival (area under curve = 0.846, 0.801, and 0.895, respectively). Functional analysis results suggested the existence of a significant association between the prognostic signature and immune-related pathways. The expression pattern of the lncRNAs was validated in AML samples.
CONCLUSION
Collectively, we constructed a prediction model based on seven cuproptosis-related lncRNAs for AML prognosis. The obtained risk score may reveal the immunotherapy response in patients with this disease.
背景
长链非编码 RNA（lncRNA）已被报道对急性髓系白血病（AML）的发病机制有重要影响。铜死亡是一种由铜触发的线粒体细胞死亡方式，可能成为癌症治疗和临床结果预测的有前途的治疗靶点。然而，铜死亡相关 lncRNA 在 AML 中的作用尚不完全清楚。
方法
从癌症基因组图谱数据库中下载 AML 患者的 RNA 测序数据和人口统计学特征。应用 Pearson 相关分析、最小绝对收缩和选择算子算法以及单变量和多变量 Cox 回归分析来识别铜死亡相关 lncRNA 特征，并确定其对 AML 预后预测的可行性。通过 Kaplan-Meier 生存分析、接收者操作特征曲线和主成分分析来评估所提出的特征的性能。进行功能分析以揭示潜在的预后机制。此外，还采用定量实时 PCR（qRT-PCR）验证 AML 样本中预后 lncRNA 的表达。
结果
提出了一个由七个铜死亡相关 lncRNA（即 NFE4、LINC00989、LINC02062、AC006460.2、AL353796.1、PSMB8-AS1 和 AC000120.1）组成的特征。多变量 Cox 回归分析表明，所提出的特征是 AML 的独立预后因素。值得注意的是，基于该特征的列线图在预测 1、3 和 5 年生存率方面表现出优异的准确性（曲线下面积分别为 0.846、0.801 和 0.895）。功能分析结果表明，预后特征与免疫相关途径之间存在显著关联。在 AML 样本中验证了 lncRNA 的表达模式。
结论
我们构建了一个基于七个铜死亡相关 lncRNA 的 AML 预后预测模型。获得的风险评分可能揭示了该疾病患者的免疫治疗反应。
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