通过多组学生物信息学分析鉴定和表征乳腺癌中铜质增生相关基因亚型。

IF 2.9 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Discover. Oncology Pub Date : 2025-02-13 DOI:10.1007/s12672-025-01952-2
Dalang Fang, Yu Zhou, Fengqing Liao, Bimin Lu, Yanghong Li, Mian Lv, Zhizhai Luo, Yanfei Ma
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摘要

cuprotosis是一种新近提出的受控细胞死亡机制,它与乳腺癌的发生和发展有着广泛的联系。本研究的目的是通过对铜质增生相关基因(cuprotosis -related genes, CRGs)表达进行全面的多组生物信息学分析,发现新的乳腺癌亚型,指导临床实践。我们收集TCGA-BRCA和GSE42568数据集来研究乳腺癌中CRGs的表达模式。进行一致聚类分析以确定不同的亚型。随后,通过功能富集分析,研究了crg簇之间的差异。最后,我们研究了微卫星不稳定性、肿瘤突变负担、药物敏感性、免疫细胞浸润和癌细胞干性。我们确定了两种亚型,其中CRGcluster S2比CRGcluster S1表现出较差的预后。此外,相对于CRGcluster S1, CRGcluster S2表现出更低的免疫浸润评分、更高的癌细胞干性指数和更高的肿瘤突变负担,其中最常见的突变基因是ATP7A。值得注意的是,与CRGcluster S1相比,乳腺癌化疗药物如多西紫杉醇、阿霉素和紫杉醇对CRGcluster S2的敏感性降低。我们已经在乳腺癌中发现了两个crg簇,它们可以作为潜在的治疗靶点,值得在乳腺癌的临床试验研究中进一步研究。
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Identification and characterization of cuproptosis related gene subtypes through multi-omics bioinformatics analysis in breast cancer.

Cuproptosis, a newly suggested mechanism of controlled cellular demise, which has been extensively associated with aspects of occurrence and development in breast cancer. The aim of this study was to conduct a comprehensive multi-group bioinformatics analysis based on the expression of cuproptosis-related genes (CRGs) to identify novel breast cancer subtypes to guide clinical practice. We collected TCGA-BRCA and GSE42568 datasets to investigate the expression patterns of CRGs in breast cancer. Consensus cluster analysis was performed to identify distinct subtypes. Subsequently, an investigation was carried out to examine the disparities between CRGclusters through functional enrichment analysis. Finally, we examined microsatellite instability, tumor mutation burden, drug sensitivity, infiltration of immune cells and cancer cell stemness across different CRGclusters. We identified two subtypes, where CRGcluster S2 exhibits a poorer prognosis compared to CRGcluster S1. Moreover, CRGcluster S2 demonstrated lower immune infiltration scores, higher cancer cell stemness index, and increased tumor mutation burden relative to CRGcluster S1, with the most frequently mutated gene being ATP7A. Notably, breast cancer chemotherapy drugs such as docetaxel, doxorubicin, and paclitaxel exhibited reduced sensitivity towards CRGcluster S2 when compared to CRGcluster S1. We have identified two CRGclusters in breast cancer that could serve as potential therapeutic targets and warrant further investigation in clinical trial studies for breast cancer.

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来源期刊
Discover. Oncology
Discover. Oncology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.40
自引率
9.10%
发文量
122
审稿时长
5 weeks
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