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基于半胱氨酸代谢-二硫键凋亡亲和力的乳腺浸润性癌患者预后分层。

Prognosis stratification of patients with breast invasive carcinoma based on cysteine metabolism-disulfidptosis affinity.

机构信息

Department of Breast Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, 510000, China.

Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, 518000, China.

出版信息

J Cancer Res Clin Oncol. 2023 Oct;149(13):11979-11994. doi: 10.1007/s00432-023-05028-y. Epub 2023 Jul 8.

Abstract

PURPOSE

The rise of female breast cancer has created a significant global public health issue that requires effective solutions. Disulfidptosis, a recently identified form of cell death characterized by an excessive accumulation of disulfides, has unique initiatory and regulatory mechanisms. The formation of disulfide bonds is a metabolic event typically associated with cysteines. This study aims to explore the potential of the affinity between cysteine metabolism and disulfidptosis in risk stratification for breast invasive carcinoma (BRCA).

METHODS

We used correlation analysis to decipher co-relation genes between cysteine metabolism and disulfidptosis (CMDCRGs). Both LASSO regression analysis and multivariate Cox regression analysis were employed to construct the prognostic signature. Additionally, we conducted investigations concerning subtype identification, functional enhancement, mutation landscape, immune infiltration, drug prioritization, and single-cell analysis.

RESULTS

We developed and validated a six-gene prognostic signature as an independent prognostic predictor for BRCA. The prognostic nomogram, based on risk score, demonstrated a favorable capability in predicting survival outcomes. We identified distinct gene mutations, functional enhancements, and immune infiltration patterns between the two risk groups. Four clusters of drugs were predicted as potentially effective for patients in the low-risk group. We identified seven cell clusters within the tumor microenvironment of breast cancer, and RPL27A was found to be widely expressed in this environment.

CONCLUSION

Multidimensional analyses confirmed the clinical utility of the cysteine metabolism-disulfidptosis affinity-based signature in risk stratification and guiding personalized treatment for patients with BRCA.

摘要

目的

女性乳腺癌的高发已成为全球重大公共卫生问题,需要有效的解决方案。二硫键过氧化物酶病(一种新发现的细胞死亡形式,其特征是二硫键过度积累)具有独特的起始和调节机制。二硫键的形成是一种通常与半胱氨酸相关的代谢事件。本研究旨在探讨半胱氨酸代谢与二硫键过氧化物酶病之间的亲和力在乳腺癌浸润性癌(BRCA)风险分层中的潜在作用。

方法

我们使用相关分析来解码半胱氨酸代谢与二硫键过氧化物酶病(CMDCRGs)之间的共相关基因。采用 LASSO 回归分析和多变量 Cox 回归分析构建预后标志。此外,我们还进行了亚组鉴定、功能增强、突变景观、免疫浸润、药物优先级和单细胞分析的研究。

结果

我们开发并验证了一个由六个基因组成的预后标志,作为 BRCA 的独立预后预测因子。基于风险评分的预后列线图显示了良好的预测生存结局的能力。我们在两个风险组之间发现了明显的基因突变、功能增强和免疫浸润模式。预测有四种药物簇可能对低风险组患者有效。我们在乳腺癌肿瘤微环境中鉴定出七个细胞簇,并且发现 RPL27A 在这个环境中广泛表达。

结论

多维分析证实了基于半胱氨酸代谢-二硫键过氧化物酶病亲和力的标志在 BRCA 风险分层和指导患者个体化治疗方面的临床应用价值。

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