基于结肠癌队列的免疫分子亚型及免疫图谱的鉴定与验证
Identification and Validation of Immune Molecular Subtypes and Immune Landscape Based on Colon Cancer Cohort.
作者信息
Qi Wenqian, Zhang Qian
机构信息
Department of Digestive, China-Japan Union Hospital, Jilin University, Changchun, China.
出版信息
Front Med (Lausanne). 2022 May 6;9:827695. doi: 10.3389/fmed.2022.827695. eCollection 2022.
BACKGROUND
The incidence and mortality rates of colon adenocarcinoma (COAD), which is the fourth most diagnosed cancer worldwide, are high. A subset of patients with COAD has shown promising responses to immunotherapy. However, the percentage of patients with COAD benefiting from immunotherapy is unclear. Therefore, gaining a better understanding of the immune milieu of colon cancer could aid in the development of immunotherapy and suitable combination strategies.
METHODS
In this study, gene expression profiles and clinical follow-up data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and molecular subtypes were identified using the package in R. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic value of immune subtypes. The graph structure learning method was used to reduce the dimension to reveal the internal structure of the immune system. Weighted correlation network analysis (WGCNA) was performed to identify immune-related gene modules. Finally, western blotting was performed to verify the gene expression patterns in COAD samples.
RESULTS
The results showed that 424 COAD samples could be divided into three subtypes based on 1921 immune cell-related genes, with significant differences in prognosis between subtypes. Furthermore, immune-related genes could be divided into five functional modules, each with a different distribution pattern of immune subtypes. Immune subtypes and gene modules were highly reproducible across many data sets. There were significant differences in the distribution of immune checkpoints, molecular markers, and immune characteristics among immune subtypes. Four core genes, namely, , , , and , with prognostic significance were identified by WGCNA and univariate Cox analysis.
CONCLUSION
Overall, this study provides a conceptual framework for understanding the tumor immune microenvironment of colon cancer.
背景
结肠腺癌（COAD）是全球第四大最常被诊断出的癌症，其发病率和死亡率都很高。一部分COAD患者对免疫疗法显示出了良好的反应。然而，受益于免疫疗法的COAD患者的比例尚不清楚。因此，更好地了解结肠癌的免疫环境有助于免疫疗法的开发和合适的联合策略。
方法
在本研究中，从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）下载了基因表达谱和临床随访数据，并使用R中的软件包鉴定分子亚型。进行单变量和多变量Cox回归分析以评估免疫亚型的预后价值。采用图结构学习方法进行降维以揭示免疫系统的内部结构。进行加权基因共表达网络分析（WGCNA）以识别免疫相关基因模块。最后，进行蛋白质免疫印迹以验证COAD样本中的基因表达模式。
结果
结果显示，424个COAD样本可根据1921个免疫细胞相关基因分为三种亚型，各亚型之间的预后存在显著差异。此外，免疫相关基因可分为五个功能模块，每个模块具有不同的免疫亚型分布模式。免疫亚型和基因模块在许多数据集中具有高度可重复性。免疫亚型之间在免疫检查点、分子标志物和免疫特征的分布上存在显著差异。通过WGCNA和单变量Cox分析鉴定出四个具有预后意义的核心基因，即 、 、 和 。
结论
总体而言，本研究为理解结肠癌的肿瘤免疫微环境提供了一个概念框架。
Zotero 插件