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Profiles of immune infiltration in colorectal cancer and their clinical significant: A gene expression‐based study

机译:大肠癌免疫浸润的概况及其临床意义:一项基于基因表达的研究

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摘要

Immune infiltration of colorectal cancer (CRC) is closely associated with clinical outcome. However, previous work has not accounted for the diversity of functionally distinct cell types that make up the immune response. In this study, based on a deconvolution algorithm (known as CIBERSORT) and clinical annotated expression profiles, we comprehensively analyzed the tumor‐infiltrating immune cells present in CRC for the first time. The fraction of 22 immune cells subpopulations was evaluated to determine the associations between each cell type and survival and response to chemotherapy. As a result, profiles of immune infiltration vary significantly between paired cancer and paracancerous tissue and the variation could characterize the individual differences. Of the cell subpopulations investigated, tumors lacking M1 macrophages or with an increased number of M2 macrophages, eosinophils, and neutrophils were associated with the poor prognosis. Unsupervised clustering analysis using immune cell proportions revealed five subgroups of tumors, largely defined by the balance between macrophages M1, M2, and NK resting cells, with distinct survival patterns, and associated with well‐established molecular subtype. Collectively, our data suggest that subtle differences in the cellular composition of the immune infiltrate in CRC appear to exist, and these differences are likely to be important determinants of both prognosis and response to treatment.
机译:大肠癌的免疫浸润与临床结局密切相关。但是,先前的工作尚未说明组成免疫应答的功能不同的细胞类型的多样性。在这项研究中,我们基于去卷积算法(称为CIBERSORT)和临床注释表达谱,首次对CRC中存在的肿瘤浸润免疫细胞进行了全面分析。评价了22个免疫细胞亚群的比例,以确定每种细胞类型与存活率和对化学疗法的反应之间的关联。结果,成对的癌症和癌旁组织之间的免疫浸润曲线显着不同,并且该变化可以表征个体差异。在所研究的细胞亚群中,缺乏M1巨噬细胞或M2巨噬细胞,嗜酸性粒细胞和嗜中性粒细胞数量增加的肿瘤与不良预后相关。使用免疫细胞比例的无监督聚类分析显示了五个肿瘤亚组,主要由巨噬细胞M1,M2和NK静止细胞之间的平衡定义,具有不同的生存模式,并与成熟的分子亚型相关。总体而言,我们的数据表明,CRC中免疫浸润的细胞组成存在细微差异,这些差异可能是决定预后和治疗反应的重要决定因素。

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