A novel prognostic signature of immune-related genes for patients with colorectal cancer
A novel prognostic signature of immune-related genes for patients with colorectal cancer
复制标题
结直肠癌患者免疫相关基因的新预后特征
DOI：
10.1111/jcmm.15443
复制
发表时间：
2020-08-01
影响因子：
5.3
通讯作者：
Chen, Jian
中科院分区：
文献类型：
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作者：
Wang, Jun;Yu, Shaojun;Chen, Jian
结直肠癌（CRC）是最常见的诊断癌症之一，全球估计有180万新发病例，2018年与88.1万例CRC相关死亡的高死亡率相关。筛查计划和新疗法仅略微改善了CRC患者的生存率。近年来，免疫相关基因（IRGs）作为治疗靶点引起了人们的关注。本研究的目的是确定一个免疫相关的预后标志为CRC。为此，我们将来自癌症基因组图谱（TCGA）的CRC数据集的基因表达和临床数据结合到一个综合免疫景观中。我们共鉴定出476个在结直肠癌和正常组织中差异表达的IRGs，根据单变量考克斯分析，其中18个与生存相关。逐步多变量考克斯比例风险分析建立了由SLC 10 A2、FGF 2、CCL 28、NDRG 1、ESM 1、UCN、UTS 2和TRDC组成的免疫相关预后标志。使用受试者工作特征（ROC）确定该特征对3年和5年总生存率的预测能力，曲线下面积（AUC）分别为79.2%和76.6%。该特征在验证和GSE 38832数据集中也显示出中等的预测准确性。单因素考克斯分析显示8-IRG与肿瘤分期、浸润深度、淋巴结转移和远处转移相关，多因素考克斯回归分析显示8-IRG是影响结直肠癌预后的独立因素。基因集富集分析（GSEA）揭示了IRG预后信号和各种生物学途径之间的关系。局灶性粘连和ECM受体相互作用与风险评分呈正相关，而细胞溶质DNA传感和代谢相关途径呈负相关。最后通过实时定量RT-qPCR对生物信息学结果进行验证。总之，我们确定并验证了CRC患者的一种新的免疫相关预后特征，这种特征反映了肿瘤免疫微环境的失调，并有可能更好地管理CRC患者。
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with an estimated 1.8 million new cases worldwide and associated with high mortality rates of 881 000 CRC-related deaths in 2018. Screening programs and new therapies have only marginally improved the survival of CRC patients. Immune-related genes (IRGs) have attracted attention in recent years as therapeutic targets. The aim of this study was to identify an immune-related prognostic signature for CRC. To this end, we combined gene expression and clinical data from the CRC data sets of The Cancer Genome Atlas (TCGA) into an integrated immune landscape profile. We identified a total of 476 IRGs that were differentially expressed in CRC vs normal tissues, of which 18 were survival related according to univariate Cox analysis. Stepwise multivariate Cox proportional hazards analysis established an immune-related prognostic signature consisting ofSLC10A2,FGF2,CCL28,NDRG1,ESM1,UCN,UTS2andTRDC. The predictive ability of this signature for 3- and 5-year overall survival was determined using receiver operating characteristics (ROC), and the respective areas under the curve (AUC) were 79.2% and 76.6%. The signature showed moderate predictive accuracy in the validation and GSE38832 data sets as well. Furthermore, the 8-IRG signature correlated significantly with tumour stage, invasion, lymph node metastasis and distant metastasis by univariate Cox analysis, and was established an independent prognostic factor by multivariate Cox regression analysis for CRC. Gene set enrichment analysis (GSEA) revealed a relationship between the IRG prognostic signature and various biological pathways. Focal adhesions and ECM-receptor interactions were positively correlated with the risk scores, while cytosolic DNA sensing and metabolism-related pathways were negatively correlated. Finally, the bioinformatics results were validated by real-time RT-qPCR. In conclusion, we identified and validated a novel, immune-related prognostic signature for patients with CRC, and this signature reflects the dysregulated tumour immune microenvironment and has a potential for better CRC patient management.