Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer.
Identification of necroptosis-related subtypes and prognosis model in triple negative breast cancer.
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DOI：
10.3389/fimmu.2022.964118
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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坏死性凋亡被认为是细胞程序性坏死的一种新形式，与各类肿瘤的转移、进展和预后相关。然而，坏死性凋亡相关基因（NRG）在三阴性乳腺癌（TNBC）中的潜在作用尚不清楚。我们从癌症基因组图谱（TCGA）数据库和基因表达综合（GEO）数据库中提取了TNBC的基因表达和相关临床病理数据。我们分析了 TNBC 中 67 个 NRG 的表达、体细胞突变和拷贝数变异 (CNV)，然后观察它们的相互作用、生物学功能和预后价值。通过Lasso和COX回归分析，构建了NRGs相关预测总生存期（OS）的风险模型，并验证了其预测能力。最后，分析了risk_score与免疫细胞浸润、肿瘤微环境（TME）、免疫检查点以及肿瘤突变负荷（TMB）、癌症干细胞（CSC）指数和药物敏感性之间的关系。我们的分析中总共鉴定出了 67 个 NRG。少数基因（23.81%）检测到体细胞突变，大部分基因出现CNV频率较高，且相互之间存在密切的相互作用。这些基因在免疫相关过程中显着丰富。生成了七基因风险评分，包含 TPSG1、KRT6A、GPR19、EIF4EBP1、TLE1、SLC4A7、ESPN。低危组的OS较好，免疫评分、TMB和CSC指数较高，TNBC常用治疗药物的IC50值较低。为了提高临床实用性，我们在risk_score中添加了年龄、stage_T和stage_N，并构建了更全面的列线图来预测OS。经验证列线图具有良好的预测能力，1年、3年、5年OS的AUC值分别为0.847、0.908、0.942。我们的研究确定了 NRG 对 TNBC 免疫和预后的显着影响。这些发现有望为 TNBC 的个性化治疗并提高其临床效益提供新策略。
Necroptosis is considered to be a new form of programmed necrotic cell death, which is associated with metastasis, progression and prognosis of various types of tumors. However, the potential role of necroptosis-related genes (NRGs) in the triple negative breast cancer (TNBC) is unclear. We extracted the gene expression and relevant clinicopathological data of TNBC from The Cancer Genome Atlas (TCGA) databases and the Gene Expression Omnibus (GEO) databases. We analyzed the expression, somatic mutation, and copy number variation (CNV) of 67 NRGs in TNBC, and then observed their interaction, biological functions, and prognosis value. By performing Lasso and COX regression analysis, a NRGs-related risk model for predicting overall survival (OS) was constructed and its predictive capabilities were verified. Finally, the relationship between risk_score and immune cell infiltration, tumor microenvironment (TME), immune checkpoint, and tumor mutation burden (TMB), cancer stem cell (CSC) index, and drug sensitivity were analyzed. A total 67 NRGs were identified in our analysis. A small number of genes (23.81%) detected somatic mutation, most genes appeared to have a high frequency of CNV, and there was a close interaction between them. These genes were remarkably enriched in immune-related process. A seven-gene risk_score was generated, containing TPSG1, KRT6A, GPR19, EIF4EBP1, TLE1, SLC4A7, ESPN. The low-risk group has a better OS, higher immune score, TMB and CSC index, and lower IC50 value of common therapeutic agents in TNBC. To improve clinical practicability, we added age, stage_T and stage_N to the risk_score and construct a more comprehensive nomogram for predicting OS. It was verified that nomogram had good predictive capability, the AUC values for 1-, 3-, and 5-year OS were 0.847, 0.908, and 0.942. Our research identified the significant impact of NRGs on immunity and prognosis in TNBC. These findings were expected to provide a new strategy for personalize the treatment of TNBC and improve its clinical benefit.
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影响因子：
7.3
作者：
Gao C;Li H;Liu C;Xu X;Zhuang J;Zhou C;Liu L;Feng F;Sun C
通讯作者：
Sun C
影响因子：
2.9
作者：
Cheng, Jia'nan;Ding, Xiaofang;Jia, Qingzhu
通讯作者：
Jia, Qingzhu
DOI：
10.1016/j.biocel.2018.10.005
发表时间：
2018-12-01
影响因子：
4
作者：
Nasr, Mostafa;Farghaly, Mohamed;Mousa, Noha
通讯作者：
Mousa, Noha
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影响因子：
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作者：
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通讯作者：
Zhu, Bo
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影响因子：
5.8
作者：
Bi, Fangfang;Chen, Ying;Yang, Qing
通讯作者：
Yang, Qing