Effect of Pyroptosis-Related Genes on the Prognosis of Breast Cancer.
Effect of Pyroptosis-Related Genes on the Prognosis of Breast Cancer.
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焦亡相关基因对乳腺癌预后的影响
DOI：
10.3389/fonc.2022.948169
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发表时间：
2022
影响因子：
4.7
通讯作者：
Lin, Nengming
中科院分区：
文献类型：
--
作者：
Zhou, Ying;Zheng, Jianfeng;Bai, Mengru;Gao, Yuzhen;Lin, Nengming
细胞凋亡是一种新的特异性程序性细胞死亡模式，已被报道参与多种癌症的发生。然而，乳腺癌（BRCA）的焦亡的价值仍然不清楚。在此，我们分析了来自癌症基因组图谱（TCGA）和GSEA MSigDB数据库的BRCA数据。基于所获得的热解相关基因，我们用STRING搜索了它们之间的相互作用。之后，我们用聚类分析软件进行聚类分析。通过单因素Cox回归筛选出具有显著预后价值的PRG，并通过最小绝对收缩选择算子（LASSO）考克斯回归构建风险模型进行进一步评估。通过综合算法预测了免疫力和药物敏感性。最后，对筛选的特征PRG中的两个进行实时定量PCR（qPCR）。从公共数据库中共获得49个PRG，其中35个为显著差异表达基因（DEG）。然后进行聚类分析，以探讨DEG与总生存率之间的关系。筛选出6个最佳PRG（GSDMC、IL-18、CHMP 3、TP 63、GZMB和CHMP 6）构建BRCA预后标志，将BRCA患者分为两个风险组。功能富集分析表明，BRCA的风险评分与肿瘤相关通路和免疫相关通路明显相关。两组中有79个微环境细胞和11个免疫检查点基因存在差异。此外，肿瘤免疫功能障碍和排斥（TIDE）评分显示，风险评分较高的患者对免疫检查点阻断治疗更敏感。低危组患者对阿糖胞苷、多西他赛、吉非替尼、紫杉醇和长春碱更敏感。然而，高危组患者对拉帕替尼更敏感。最后，我们发现CHMP 3在BRCA组织和细胞系中均下调，而IL-18则上调。PRG在BRCA中发挥重要作用。本研究填补了6个PRG在BRCA中的空白，作为预测潜在生物标志物和治疗靶点值得进一步研究。
Pyroptosis, a newly pattern of specific programmed cell death, has been reported to participate in several cancers. However, the value of pyroptosis in breast cancer (BRCA) is still not clear. Herein, we analyzed the data of BRCA from both The Cancer Genome Atlas (TCGA) and GSEA MSigDB database. Based on the obtained pyroptosis-related genes (PRGs), we searched the interactions by STRING. After that, we performed clustering analysis by ConsensusClusterPlus. The PRGs with significant prognostic value were then screened through univariate cox regression and further evaluate by constructing a risk model by least absolute shrinkage and selection operator (LASSO) Cox regression. The immune and sensitivity to drugs were also predicted by comprehensive algorithms. Finally, real-time quantitative PCR (qPCR) was performed on two of the screened signature PRGs. A total of 49 PRGs were obtained from public database and 35 of them were significantly differentially expressed genes (DEGs). Cluster analysis was then performed to explore the relationship between DEGs with overall survival. After that, 6 optimal PRGs (GSDMC, IL-18, CHMP3, TP63, GZMB and CHMP6) were screened out to construct a prognostic signature, which divide BRCA patients into two risk groups. Risk scores were then confirmed to be independent prognostic factors in BRCA. Functional enrichment analyses showed that the signature were obviously associated with tumor-related and immune-associated pathways. 79 microenvironmental cells and 11 immune checkpoint genes were found disparate in two groups. Besides, tumor immune dysfunction and exclusion (TIDE) scores revealed that patients with higher risk scores are more sensitive to immune checkpoint blockade treatment. Patients in the low-risk group were more sensitive to Cytarabine, Docetaxel, Gefitinib, Paclitaxel, and Vinblastine. Inversely, patients in the high-risk group were more sensitive to Lapatinib. Finally, we found that, CHMP3 were down-regulated in both BRCA tissues and cell lines, while IL-18 were up-regulated. PRGs play important roles in BRCA. Our study fills the gaps of 6 selected PRGs in BRCA, which were worthy for the further study as predict potential biomarkers and therapeutic targets.
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影响因子：
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作者：
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通讯作者：
Kanneganti TD
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Clarke, Colin;Madden, Stephen F.;Clynes, Martin
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Gregory Sorensen A