Department of Gastrointestinal Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Department of General, Visceral, and Transplant Surgery, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
Front Immunol. 2020 Sep 3;11:1678. doi: 10.3389/fimmu.2020.01678. eCollection 2020.
Increasing studies have highlighted the effects of the tumor immune micro-environment (TIM) on colon cancer (CC) tumorigenesis, prognosis, and metastasis. However, there is no reliable molecular marker that can effectively estimate the immune infiltration and predict the CC relapse risk. Here, we leveraged the gene expression profile and clinical characteristics from 1430 samples, including four gene expression omnibus database (GEO) databases and the cancer genome atlas (TCGA) database, to construct an immune risk signature that could be used as a predictor of survival outcome and immune activity. A risk model consisting of 10 immune-related genes were screened out in the Lasso-Cox model and were then aggregated to generate the immune risk signature based on the regression coefficients. The signature demonstrated robust prognostic ability in discovery and validation datasets, and this association remained significant in the multivariate analysis after controlling for age, gender, clinical stage, or microsatellite instability status. Leukocyte subpopulation analysis indicated that the low-risk signature was enriched with cytotoxic cells (activated CD4/CD8 T cell and NK cell) and depleted of myeloid-derived suppressor cells (MDSC) and regulatory T cells. Further analysis indicated patients with a low-risk signature harbored higher tumor mutation loads and lower mutational frequencies in significantly mutated genes of and . Together, our constructed signature could predict prognosis and represent the TIM of CC, which promotes individualized treatment and provides a promising novel molecular marker for immunotherapy.
越来越多的研究强调了肿瘤免疫微环境(TIM)对结肠癌(CC)发生、预后和转移的影响。然而,目前还没有可靠的分子标志物能够有效地评估免疫浸润程度并预测 CC 的复发风险。在这里,我们利用了来自 1430 个样本的基因表达谱和临床特征,包括四个基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库,构建了一个免疫风险特征,可以作为生存结果和免疫活性的预测因子。在 Lasso-Cox 模型中筛选出由 10 个免疫相关基因组成的风险模型,然后根据回归系数聚合生成免疫风险特征。该特征在发现和验证数据集均具有稳健的预后能力,并且在控制年龄、性别、临床分期或微卫星不稳定性状态后,在多变量分析中仍然具有显著意义。白细胞亚群分析表明,低风险特征富含细胞毒性细胞(激活的 CD4/CD8 T 细胞和 NK 细胞),并减少髓系来源的抑制细胞(MDSC)和调节性 T 细胞。进一步分析表明,低风险特征的患者具有更高的肿瘤突变负荷和较低的显著突变基因中的突变频率。总之,我们构建的特征可以预测预后并代表 CC 的 TIM,这促进了个体化治疗,并为免疫治疗提供了有前途的新的分子标志物。