基于癌症免疫周期筛选结直肠癌免疫联合治疗的新靶点  

Screening novel targets for combination immunotherapy of colorectal cancer based on cancer immune cycle

作　　者：曾薇 唐菊彬 陈向宙 陈玮[1] 杨丹[1] 朱金峰 ZENG Wei;TANG Jubin;CHEN Xiangzhou;CHEN Wei;YANG Dan;ZHU Jinfeng(The Forth Department of Cancer Center,the Sixth Affiliated Hospital of South China University of Technology,Foshan,Guangdong 528200,China;不详)

机构地区：[1]华南理工大学附属第六医院肿瘤医学中心四区,广东佛山528200 [2]华南理工大学附属第六医院胃肠外科,广东佛山528200

出　　处：《中华全科医学》2025年第1期31-35,147,共6页Chinese Journal of General Practice

基　　金：国家自然科学基金青年科学基金项目(82103636);广东省基础与应用基础研究基金自然科学基金项目(2022A1515012613)。

摘　　要：目的目前免疫检查点抑制剂(ICI)已批准用于治疗不可切除或转移性高度微卫星不稳定型/错配修复缺陷型(dMMR/MSI-H型)结直肠癌患者。然而,约50%的dMMR/MSI-H型患者对ICI原发性耐药,而MSS/pMMR型患者对单药ICI的反应有限,因此目前亟待寻找免疫联合治疗的新靶点,进一步改善患者ICI的治疗疗效。方法本研究将癌症免疫周期评分与加权基因共表达网络和系统分析相结合,以筛选结直肠癌中的免疫抑制基因;使用GEPIA2数据库分析基因在结直肠癌组织中的表达特征;CIBERSORT评估基因表达与免疫细胞浸润水平的相关性;TIDE算法预测基因表达与患者免疫治疗疗效的关系;Kaplan-Meier生存分析比较基因高、低表达水平组接受免疫治疗后的预后差异;GSEA分析基因参与结直肠癌的发生、发展,影响患者预后的调控机制。结果癌症免疫周期评分、加权基因共表达网络和系统分析提示DDX 27是结直肠癌免疫联合治疗的新靶点;DDX 27在结直肠癌组织中呈显著高表达(P<0.001),与患者较晚的N分期(P=0.005)、TNM分期(P=0.006)和抑制性免疫细胞的浸润水平呈正相关关系;DDX 27高水平表达组患者接受免疫治疗的疗效不佳,且该组患者接受ICI治疗后的总生存期短于DDX 27低水平表达组(7.2个月vs.9.6个月);进一步分析显示DDX 27可能通过调控RNA加工、代谢参与结直肠癌的发生、发展,影响患者的预后。结论鉴于DDX 27可能通过促进抑制性免疫细胞浸润,调控RNA加工和代谢参与结直肠癌的发生、发展,因此靶向干扰DDX 27可能作为结直肠癌免疫联合治疗的新策略。Objective At this stage,immune checkpoint inhibitors(ICIs)are approved for the treatment of colorectal cancer.However,about 50%of dMMR/MSI-H-type patients are primarily resistant to ICIs,and MSS/pMMR-type patients have limited response to single-agent ICIs;therefore,there is an urgent need to find new targets for immune-combination therapy to further improve the therapeutic efficacy of ICIs in patients.Methods In this study,we combined the Cancer Immune Cycle Score with the weighted gene co-expression network and systematic analyses to screen immunosuppressive genes in colorectal cancer;analyzed gene expression profiles in colorectal cancer tissues using the GEPIA2 database;CIBERSORT assessed the correlation between gene expression and the level of immune cell infiltration;the TIDE algorithm predicted the gene expression in relation to the efficacy of patient immunotherapy relationship;Kaplan-Meier survival analysis to compare the prognostic differences between groups with high and low expression levels of genes after receiving immunotherapy;and GSEA to analyze the regulatory mechanisms of genes involved in colorectal cancer genesis,development,and affecting the prognosis of patients.Results Cancer immune cycle score with weighted gene co-expression network and systematic analysis showed that DDX 27 was an immunosuppressive target of colorectal cancer;DDX 27 was significantly highly expressed in colorectal cancer tissues(P<0.001),which was positively correlated with the patients'later N stage(P=0.005),TNM stage(P=0.006)and infiltration level of suppressive immune cells;patients in the group with high levels of DDX 27 expression were poorly treated with immunotherapy,and the overall survival of patients in this group treated with ICI was shorter than that in the group with low levels of DDX 27 expression(7.2 months vs.9.6 months);further analysis showed that DDX 27 might be involved in the occurrence and development of colorectal cancer through the regulation of RNA processing and metabolism,and affect the prognos

关 键 词：结直肠癌 癌症免疫周期 免疫治疗 

分 类 号：R735.35[医药卫生—肿瘤] R735.37[医药卫生—临床医学]