Zhang Bingxin, Zhu Shuxia, Zheng Dong, Zhang Xinyi, Xie Wenxia, Zhou Shujuan, Zheng Sisi, Wang Quanqiang, Lin Zhili, Zheng Ziwei, Chen Zixing, Lan Enqing, Cui Luning, Ying Hansen, Zhang Yu, Lin Xuanru, Zhuang Qiang, Qian Honglan, Hu Xudong, Zhuang Yan, Zhang Qianying, Jin Zhouxiang, Jiang Songfu, Ma Yongyong
Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Eur J Med Res. 2025 May 31;30(1):435. doi: 10.1186/s40001-025-02572-w.
Cuproptosis is a brand-new copper-dependent type of cell death that has been linked to various tumors. However, the relationship between cuproptosis and acute lymphoblastic leukemia (ALL) remains to be further elaborated.
In ALL, 12 cuproptosis-related genes (CRGs) were analyzed at genetic and single-cell levels. Two molecular clusters were identified using "ConsensusClusterPlus". With the least absolute shrinkage and selection operator, a prognostic signature was built based on cuproptosis. The prognosis, clinical parameters, biological function, immune cell infiltration, therapy sensitivities, and transcription factor regulation of the clusters and risk subsets were further compared. Kaplan Meier curves, time-ROC curves, and nomogram were employed to evaluate the accuracy of the signature. Lastly, qRT-PCR was used to detect prognostic genes in cell lines and clinical samples.
CRGs exhibited extensive genetic variations and heterogeneous expression profiles in ALL. Single-cell analysis demonstrated that CRGs were strongly correlated with the biological characteristics of cancer cells. Two clusters and risk subgroups with distinct clinicopathological features, prognoses, biological functions, and drug sensitivities were identified. The cuproptosis signature was crucial in characterizing tumor immune landscape and cancer cell self-renewal ability. Furthermore, we explored that subtype A and high-scoring groups were more sensitive to immunotherapy. Multiple drugs with higher sensitivity among high-risk subgroups have been predicted. Nomograms demonstrated the clinical applicability of cuproptosis in risk assessment. The model was further validated in the verification cohort, our clinical specimens, and cell lines.
The cuproptosis-based model can characterize the tumor microenvironment, forecast survival results, and aid in improving risk assessment and personalized therapy options in ALL.
铜死亡是一种全新的铜依赖性细胞死亡类型，已被证明与多种肿瘤相关。然而，铜死亡与急性淋巴细胞白血病（ALL）之间的关系仍有待进一步阐明。
在ALL中，对12个铜死亡相关基因（CRGs）进行了基因和单细胞水平的分析。使用“ConsensusClusterPlus”鉴定出两个分子簇。利用最小绝对收缩和选择算子，基于铜死亡构建了一个预后特征。进一步比较了这些簇和风险亚组的预后、临床参数、生物学功能、免疫细胞浸润、治疗敏感性和转录因子调控。采用Kaplan Meier曲线、时间ROC曲线和列线图来评估该特征的准确性。最后，使用qRT-PCR检测细胞系和临床样本中的预后基因。
CRGs在ALL中表现出广泛的基因变异和异质性表达谱。单细胞分析表明，CRGs与癌细胞的生物学特征密切相关。鉴定出两个具有不同临床病理特征、预后、生物学功能和药物敏感性的簇和风险亚组。铜死亡特征在表征肿瘤免疫格局和癌细胞自我更新能力方面至关重要。此外，我们发现A亚型和高分群体对免疫治疗更敏感。预测了高危亚组中多种敏感性较高的药物。列线图证明了铜死亡在风险评估中的临床适用性。该模型在验证队列、我们的临床标本和细胞系中得到了进一步验证。
基于铜死亡的模型可以表征肿瘤微环境，预测生存结果，并有助于改善ALL的风险评估和个性化治疗方案。
