研究动态
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铜肝细胞凋亡标记的泛癌模式揭示了生物学上和临床上相关的癌症亚型。

Pan-cancer patterns of cuproptosis markers reveal biologically and clinically relevant cancer subtypes.

发表日期:2023 Jan 31
作者: Fanqin Bu, Xiangji Li, Yu Zhao, Liyi Bai, Shutian Zhang, Li Min
来源: Biomarker Research

摘要:

Cuproptosis 是一种新发现的由铜积累触发的细胞死亡类型。在此,我们展示了 10 个与 Cuproptosis 相关的基因 (CuAGs) 在 21 种癌症类型中的基因型。仅有 8.0% 的肿瘤 (627/7839) 至少拥有 1 种 CuAGs 的突变,而 CuAGs 等位基因的拷贝数扩增或缺失是普遍存在的。总的来说,CuAGs 的表达在癌症类型间显示异质性,并且 CuAGs 的表达在不同癌症类型中与 MSI、TMB、免疫和基质特征显示不同的相关性。因此,CuAGs 在泛癌症中广泛且异质地发生了调节失常。采用非负矩阵分解方法,我们将每个癌症类型的患者分为基于 cuproptosis 的亚型,并且这些亚型与不同的生物学和临床特征呈密切但具有异质性的相关性。因此,我们将所有癌症类型总结为四种类别。与 MSI 和 TMB 相关的 cuproptosis 亚型被注释为遗传紊乱型,与基质评分相关的被归类为基质重构型,只与免疫浸润相关的被标记为免疫抑制型。未与任何生物学指标相关的少部分癌症被标记为 Cuproptosis 惰性型。综上所述,我们提供了 Cuproptosis 标志物的泛癌症概述,揭示了不同癌症中具有生物学和临床相关性的癌症亚型。©2023年作者(们).
Cuproptosis is a newly discovered type of cell death triggered by copper accumulation. Here we exhibited the genetic profiles of 10 cuproptosis-associated genes (CuAGs) across 21 cancer types. Only 8.0% (627/7839) of tumors possessed at least 1 mutation on CuAGs, while the copy number amplifications or deletions on the alleles of CuAGs were ubiquitous. Generally, the expression of CuAGs showed heterogeneity across cancer types and the expression of CuAGs showed different correlations with MSI, TMB, immune and stromal features in different cancer types. Therefore, CuAGs were ubiquitously and heterogeneously dysregulated in pan-cancer. With a Non-negative Matrix Factorization method, we divided patients of each cancer type into cuproptosis-based subtypes, which showed a close but heterogeneous correlation with different biological and clinical features. Accordingly, we summarized all cancer types into four categories. The cancers in which cuproptosis subtypes correlated with MSI and TMB were annotated as Genomic disturbed. Those correlated with stromal scores were categorized as Stromal remolded. The others only associated with immune infiltration were labeled as Immune inhibited. A minor fraction of cancers not correlated with any biological indicators were marked as Cuproptosis inert. Together, we provided a pan-cancer overview of cuproptosis markers which revealed biologically and clinically relevant cancer subtypes in different cancers.© 2023. The Author(s).