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基于免疫图谱的预后标志物可预测结直肠癌患者的免疫状态和免疫治疗反应。

An immune landscape based prognostic signature predicts the immune status and immunotherapeutic responses of patients with colorectal cancer.

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan, China.

Department of Medical Records, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China.

出版信息

Life Sci. 2020 Nov 15;261:118368. doi: 10.1016/j.lfs.2020.118368. Epub 2020 Sep 1.

Abstract

AIMS

Colorectal cancer (CRC) is one of the most common cancers with poor prognosis worldwide. The advent of immunotherapy has greatly improved survival in refractory patients of CRC. In this study, we aimed to identify reliable immune classification and biomarkers that predict immunotherapeutic responses in CRC patients.

MATERIALS AND METHODS

Based on transcriptome profiles of two publicly available CRC datasets, we performed single-sample gene set enrichment analysis (ssGSEA) to calculate the relative abundance of 29 immune-related items of each sample. Unsupervised clustering was used to classify CRC patients. Furthermore, an immune prognostic signature was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis.

KEY FINDINGS

The CRC patients were clustered into high, medium, low immune infiltration subtypes based on the immune landscape. There was significant heterogeneity among the three subtypes. The high immune infiltration group showed higher expression of programmed cell death-ligand 1 and better prognosis than the median and low immune infiltration groups. Furthermore, we constructed a 7-immune-related prognostic gene signature and found that the signature had high predictive value and was superior to other clinicopathological parameters. Finally, the correlation analysis of the signature with immune cell infiltration and immune checkpoint molecules suggested that the signature had the potential to assess the immunotherapeutic responses of CRC patients.

SIGNIFICANCE

The immune landscape and prognostic signature of CRC contribute to a deeper understanding of the tumor microenvironment and guide accurate immunotherapy.

摘要

目的

结直肠癌(CRC)是全球最常见的预后不良的癌症之一。免疫疗法的出现极大地改善了 CRC 耐药患者的生存率。在本研究中,我们旨在确定可靠的免疫分类和生物标志物,以预测 CRC 患者的免疫治疗反应。

材料和方法

基于两个公开可用的 CRC 数据集的转录组谱,我们进行了单样本基因集富集分析(ssGSEA),以计算每个样本 29 种免疫相关项目的相对丰度。使用无监督聚类对 CRC 患者进行分类。此外,使用最小绝对收缩和选择算子(LASSO)Cox 回归分析构建免疫预后签名。

主要发现

根据免疫图谱,CRC 患者被聚类为高、中、低免疫浸润亚型。这三个亚型之间存在显著的异质性。高免疫浸润组程序性细胞死亡配体 1 的表达较高,预后优于中、低免疫浸润组。此外,我们构建了一个 7 个免疫相关的预后基因签名,并发现该签名具有较高的预测价值,优于其他临床病理参数。最后,对签名与免疫细胞浸润和免疫检查点分子的相关性分析表明,该签名具有评估 CRC 患者免疫治疗反应的潜力。

意义

CRC 的免疫图谱和预后签名有助于更深入地了解肿瘤微环境,并指导准确的免疫治疗。

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