Identification and validation of a pyroptosis-related prognostic model for colorectal cancer
Identification and validation of a pyroptosis-related prognostic model for colorectal cancer
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DOI：
10.1007/s10142-022-00935-8
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发表时间：
2023-03-01
影响因子：
2.9
通讯作者：
Liu，Gang
中科院分区：
文献类型：
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作者：
Li，Ruibin;Zhang，Shiyao;Liu，Gang
在这项研究中，我们探讨了大肠癌（CRC）的热解相关的生物标志物和签名。基因表达谱从Gene Expression Omnibus（GEO）和The Cancer Genome Atlas（TCGA）-COADREAD下载，并分析差异表达基因（DEG）。通过交叉与CRC和PRG相关的DEG获得CRC热解相关基因（CRC_PRG）中的DEG。验证CRC CRP-PRG;用基因本体（GO）进行功能富集分析，然后进行聚类分析。对TCGA数据集进行考克斯分析和LASSO回归，以构建CRC患者的预后模型。构建预后风险评估模型并评价疗效。决策曲线分析用于评估Lasso-Cox回归预后模型在1年、3年和5年时的临床效用。12个CRC PRG被鉴定为预后性脓毒性相关DEG，CXCL 8、IL 13 RA 2、MELK和POP 1被选择为预后性基因，以构建在GEO和TCGA中具有良好预后性能的特征。功能富集表明，4-基因标签可能通过多种途径参与CRC肿瘤的发生和发展，在CRC中发挥预后作用。此外，免疫景观分析结果显示，CXCL 8和IL 13 RA 2在TCGA-COADREAD数据集中的表达与大多数免疫细胞的显著差异富集呈正相关。由CXCL 8、IL 13 RA 2、MELK和POP 1四个关键基因组成的新的预后模型可以准确预测CRC患者的生存期。这一发现可能为治疗脓毒性相关的结直肠癌提供新的视角。
In this study, we explored the pyroptosis-related biomarkers and signatures of colorectal cancer (CRC). Gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA)-COADREAD and were analyzed for differentially expressed genes (DEGs). DEGs in CRC‒pyroptosis-related genes (CRC‒PRGs) were obtained by intersecting DEGs associated with CRC and PRGs. The CRC‒PRGs were verified; functional enrichment analysis was performed with Gene Ontology (GO) followed by cluster analysis. Cox analyses and LASSO regression were used in TCGA dataset to construct a prognostic model for patients with CRC. A prognostic risk assessment model was constructed and efficacy was evaluated. Decision curve analysis was utilized to assess the role of the Lasso-Cox regression prognostic model for clinical utility at 1, 3, and 5 years. Twelve CRC‒PRGs were identified as prognostic pyroptosis-related DEGs.CXCL8,IL13RA2,MELK, andPOP1were selected as prognostic genes to construct features with a good prognostic performance in GEO and TCGA. Functional enrichment indicated that the 4-gene signature might be involved in CRC tumorigenesis and development through various pathways by playing a prognostic role in CRC. Furthermore, the results of the immune landscape analysis showed that the expression ofCXCL8andIL13RA2in TCGA-COADREAD dataset was positively correlated with significant differential enrichment of most immune cells. A novel prognostic model consisting of four key genes,CXCL8,IL13RA2,MELK, andPOP1, can accurately predict the survival of patients with CRC. This finding may provide a new perspective for the treatment of pyroptosis-related CRC.