Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of colorectal cancer
Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of colorectal cancer
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DOI：
10.1016/j.biopha.2019.109228
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发表时间：
2019-10-01
影响因子：
7.5
通讯作者：
Wu, Yang
中科院分区：
文献类型：
--
作者：
Ge, Penglei;Wang, Weiwei;Wu, Yang
目的：肿瘤浸润性免疫细胞与结直肠癌（CRC）的进展和预后密切相关。本研究旨在探讨结直肠癌肿瘤微环境中免疫细胞及免疫相关基因的表达情况。方法：采用CIBERSORT反卷积算法，分析404例结直肠癌及40例癌旁组织中22种免疫细胞在肿瘤微环境中的浸润情况及免疫相关基因的表达情况。揭示了不同配对组织和肿瘤阶段中免疫细胞的广泛异质性。在TCGA和GEO队列中，与正常组织相比，M0巨噬细胞、M1巨噬细胞和CD 4记忆激活的T细胞在CRC中的浸润显著更多。与T3-4肿瘤相比，具有T1-2肿瘤分期的CRC显示增加的CD 4记忆激活的T细胞。M0巨噬细胞在N1期肿瘤中最高。通过考克斯回归分析确定与免疫相关的基因，建立预后模型。TNM分期I-II的预后模型的一致性指数为0.69，III-IV期为0.71。TNM Ⅰ ~ Ⅱ期1、3、5年生存率AUC分别为0.674、0.773、0.812，Ⅲ ~ Ⅳ期分别为0.764、0.782、0.803。结论：本研究结果可为临床选择免疫治疗靶点和个体化治疗策略提供参考。
Purpose: tumor-infiltrating immune cells are highly relevant to the progression and prognosis of colorectal cancer (CRC). The aim of this study is to explore the immune cells and immune-related gene expression in tumor microenvironment of CRC.Methods: CIBERSORT, a deconvolution algorithm, was used to analyze the infiltration of 22 immune cell types in the tumor microenvironment and immune-related gene expression in 404 CRC and 40 adjacent non-tumorous tissues.Results: a wide heterogeneity of immune cells among different paired tissues and in tumor stages was uncovered. M0 macrophages, M1 macrophages and CD4 memory activated T cells were infiltrated significantly more in CRC compared with normal tissues in both TCGA and GEO cohorts. CRC with T1-2 tumor stage showed increased CD4 memory activated T cells compared with T3-4 tumors. M0 macrophages were the highest in stage N1 tumors. Significant immune-related genes were identified to build prognostic models by Cox regression analysis. The concordance index of the prognostic model for TNM stage I-II was 0.69, and 0.71 for stage III-IV. The AUC values for 1-, 3-, and 5-year survivals were 0.674, 0.773, 0.812 for TNM stage I-II, respectively, and 0.764, 0.782, 0.803 for stage III-IV respectively.Conclusion: these results could assist clinicians in selecting targets for immunotherapies and individualize treatment strategies for patients with CRC.