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Molecular subtyping and immune score system by a novel pyroptosis-based gene signature precisely predict immune infiltrating, survival and response to immune-checkpoint blockade in breast cancer
Cancer Genetics ( IF 1.9 ) Pub Date : 2023-07-21 , DOI: 10.1016/j.cancergen.2023.07.007
Xiaomei Zeng 1 , Xun Huang 2 , Lingxi Yin 1 , Hui Yu 1 , Shiyu Wang 1 , Lijuan Li 1
Affiliation  

Breast cancer is one of the most prevalent and lethal types of cancer affecting women globally. Pyroptosis is a recently elucidated form of inflammatory cell death mediated by the gasdermin family and is considered to be associated with the tumor immune microenvironment. However, the impact of pyroptosis on breast cancer patients remains unclear. In this study, we identified 31 Pyroptosis-Related-Genes (PRGs) and investigated their association with patient survival using data from the TCGA database. We then established a gene signature comprising 6 PRGs that were significantly correlated with prognosis, and used these genes to classify breast cancer into 2 molecular subtypes. We investigated the characteristics of these two subtypes and found that our molecular subtyping accurately separated the samples into two groups with distinct immune infiltration and prognosis. Patients with higher expression of these genes had significantly greater immune infiltrating, T cell signaling, and better prognosis. Moreover, we developed an immune score system based on these 6 genes that accurately predicted the immune infiltrating of patients and their response to immune-checkpoint blockade, which was difficult to achieve with previous models. Additionally, through single-cell analyses, we found that patients with higher immune scores had stronger cytotoxic immune cells. In summary, our study identified a novel gene set and developed an immune scoring system based on this gene set that can precisely predict the immune microenvironment and responses to immunotherapy of breast cancer (BRCA) patients, which could be useful in clinical trials.



中文翻译:

基于新型焦亡基因特征的分子亚型和免疫评分系统可精确预测乳腺癌的免疫浸润、存活和对免疫检查点封锁的反应

乳腺癌是影响全球女性的最流行和最致命的癌症类型之一。焦亡是最近阐明的由gasdermin家族介导的炎症细胞死亡的一种形式,被认为与肿瘤免疫微环境有关。然而,焦亡对乳腺癌患者的影响仍不清楚。在这项研究中,我们鉴定了 31 个焦亡相关基因 (PRG),并使用 TCGA 数据库中的数据研究了它们与患者生存的关联。然后,我们建立了包含 6 个与预后显着相关的 PRG 的基因特征,并使用这些基因将乳腺癌分为 2 个分子亚型。我们研究了这两种亚型的特征,发现我们的分子亚型准确地将样本分为两组,具有不同的免疫浸润和预后。这些基因表达较高的患者具有明显更强的免疫浸润、T 细胞信号传导和更好的预后。此外,我们开发了基于这6个基因的免疫评分系统,可以准确预测患者的免疫浸润及其对免疫检查点封锁的反应,这是以前的模型难以实现的。此外,通过单细胞分析,我们发现免疫评分较高的患者具有更强的细胞毒性免疫细胞。总之,我们的研究确定了一个新的基因集,并基于该基因集开发了一个免疫评分系统,可以精确预测乳腺癌(BRCA)患者的免疫微环境和免疫治疗反应,这在临床试验中可能有用。

更新日期:2023-07-21
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