A pairwise immune gene model for predicting overall survival and stratifying subtypes of colon adenocarcinoma
作者全名："Jiang, Ziyuan; Xu, Jie; Zhang, Sitong; Lan, Haiyan; Bao, Yixi"
作者地址："[Jiang, Ziyuan; Xu, Jie; Zhang, Sitong; Lan, Haiyan; Bao, Yixi] Chongqing Med Univ, Dept Clin Lab, Affiliated Hosp 2, Chongqing 400010, Peoples R China"
通信作者："Bao, YX (通讯作者)，Chongqing Med Univ, Dept Clin Lab, Affiliated Hosp 2, Chongqing 400010, Peoples R China."
来源：JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ESI学科分类：CLINICAL MEDICINE
WOS号：WOS:001007983600001
JCR分区：Q3
影响因子：2.7
年份：2023
卷号：
期号：
开始页：
结束页：
文献类型：Article; Early Access
关键词：Immune landscape; Subtype; Gene pair; Prognosis; Immunotherapy
摘要："ObjectivesThere is increasing evidence for a close correlation between risk stratification, prognosis and the immune environment in colon adenocarcinoma (COAD). However, the efficacy of immunotherapy is different among different patients with COAD. Therefore, the current work tends to use immune-related gene to develop a gene-pair model to evaluate the COAD prognosis, and to develop a new method for risk stratification of COAD, which is conducive to better predict the immunotherapy effect of patients.MethodsSpecifically, from the TCGA and GEO (GSE14333 and GSE39582) databases, we first collected gene expression profiles, associated survival follow-up information of COAD patients. Through systematic bioinformatics analysis, we established a prognosis-related model of colon cancer with three pairs of ""immune gene pairs"", with uni- and multivariate and lasso cox regression analyses verifying the model stability. Most immune cells showed markedly different levels of infiltration between the two risk subgroups calculated by the model. More, single-cell RNA-seq analyses were also performed to validate the selected genes in the immune gene-pair model.ResultsA prognosis-related model of colon cancer with three pairs of ""immune gene pairs"" were built and validated by several datasets. The analysis of immune landscape of COAD revealed that low-risk subgroup obtained by the prognosis-related model for COAD can be further divided into three subclusters with different prognosis. Then, we applied the Tumor online Prognostic analyses Platform (ToPP) to construct a prognostic model using these five genes. Results show that APOD, ISG20 and STC2 are risk factors, while CXCL9 and IL7R are protection factors. We also found that only the five-gene model could also predict the prognosis of COAD patients, indicating the robustness of the gene-pair model. Among the five genes, including CXCL9, APOD, STC2, ISG20, and IL7R, in the gene-pair model, single-cell RNA sequencing reveals the high expression of CXCL9 and IL7R in inflammatory macrophages. Using cell-cell interaction and trajectory analysis, data indicate that CXCL9(+)/IL7R(+) pro-inflammatory macrophages were capable of secreting and activating more anti-tumor pathways than CXCL9(-)/IL7R(-) pro-inflammatory macrophages.ConclusionsIn short, we have successfully developed an ""immune gene pair"" related model that can judge the prognostic status of patients with COAD and may contribute to risk stratification and evaluate potential beneficiaries of immunotherapy, providing new ideas for the anti-COAD management and therapy."
基金机构：Natural Science Foundation of Chongqing of China [cstc2021jcyj-msxmX0094]; National Natural Science Foundation of China [81773940]
基金资助正文：This work was supported by the Natural Science Foundation of Chongqing of China (No. cstc2021jcyj-msxmX0094) and the National Natural Science Foundation of China (No. 81773940).
