Mo Xianwei, Huang Xiaoliang, Feng Yan, Wei Chunyin, Liu Haizhou, Ru Haiming, Qin Haiquan, Lai Hao, Wu Guo, Xie Weishun, Jeen Franco, Lin Yuan, Liu Jungang, Tang Weizhong
Division of Colorectal & Anal Surgery,Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, the People's Republic of China.
Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, the People's Republic of China.
Oncoimmunology. 2020 Oct 19;9(1):1832347. doi: 10.1080/2162402X.2020.1832347.
Fluoropyrimidine-based chemotherapy is an essential component of systemic chemotherapy for colorectal cancer (CRC). The immune response is implicated in chemotherapy-induced cytotoxicity. Here, we reported an immune risk (Imm-R) model for prognostic prediction in patients receiving fluoropyrimidine-based chemotherapy. Gene expression profiles and corresponding clinical information were collected from four data sets and divided into training set (n = 183) and validation set (validation set1: n = 34; validation set2: n = 99). The composition of 22 tumor-infiltrating immune cells (TIICs) populations was characterized with the CIBERSORT deconvolution algorithm. A prognostic Imm-R model for predicting overall survival was established by performing least absolute shrinkage and selection operator (LASSO) penalized COX regression analysis. T follicular helper cells and M0 macrophages were associated with better survival, while eosinophils were associated with worse survival. TIICs signature was constructed based on the above three immune cell types. Furthermore, a Imm-R model was created by integrating TIICs signature with immune-related genes (IRGs), which effectively in distinguishing CRC patients with poorer prognosis. The Imm-R model was associated with activation of the TGF-beta signaling and suppression of DNA damage. Results of this research provide new insights into the role of immunity for in fluoropyrimidine-based chemotherapy as well as a useful tools to predict the outcome of CRC patients receiving fluoropyrimidine-based chemotherapy.
基于氟嘧啶的化疗是结直肠癌（CRC）全身化疗的重要组成部分。免疫反应与化疗诱导的细胞毒性有关。在此，我们报告了一种用于接受基于氟嘧啶化疗患者预后预测的免疫风险（Imm-R）模型。从四个数据集收集基因表达谱和相应的临床信息，并分为训练集（n = 183）和验证集（验证集1：n = 34；验证集2：n = 99）。用CIBERSORT反卷积算法对22种肿瘤浸润免疫细胞（TIIC）群体的组成进行了表征。通过进行最小绝对收缩和选择算子（LASSO）惩罚COX回归分析，建立了预测总生存期的预后Imm-R模型。滤泡辅助性T细胞和M0巨噬细胞与较好的生存率相关，而嗜酸性粒细胞与较差的生存率相关。基于上述三种免疫细胞类型构建了TIIC特征。此外，通过将TIIC特征与免疫相关基因（IRG）整合创建了一个Imm-R模型，该模型有效地区分了预后较差的CRC患者。Imm-R模型与TGF-β信号通路的激活和DNA损伤的抑制有关。本研究结果为免疫在基于氟嘧啶化疗中的作用提供了新的见解，并为预测接受基于氟嘧啶化疗的CRC患者的预后提供了有用的工具。
