细胞周期蛋白A2调控肿瘤细胞免疫微环境对结肠癌预后的影响  

Effect of CCNA2 on Prognosis of Colon Cancer by Regulating Immune Microenvironment of Tumor Cells

作　　者：杨鹏[1] 邱子奕 王灵灵 胡园 陈峥桢 钟美珍 余飞跃[1] 邱荣元[1] YANG Peng;QIU Ziyi;WANG Lingling;HU Yuan;CHEN Zhengzhen;ZHONGMeizhen;YU Feiyue;QIU Rongyuan(Department of Gastroenterology,Yueyang Hospital Affiliated to Hunan Normal University,Yueyang 414000,China;Department of Gastroenterology,The 2nd Affiliated Hospital of Xinjiang Medical University,Urumqi 830018,China)

机构地区：[1]湖南师范大学附属岳阳医院消化内科,岳阳414000 [2]新疆医科大学第二附属医院消化内科,乌鲁木齐830018

出　　处：《肿瘤防治研究》2025年第4期305-312,共8页Cancer Research on Prevention and Treatment

摘　　要：目的从免疫浸润角度探讨细胞周期蛋白A2(CCNA2)与结肠癌预后的关系及可能机制。方法从癌症基因组图谱数据库下载结肠癌患者转录组数据。根据CCNA2表达情况进行临床病理特征分析及生存分析。收集75例结肠癌患者术后肿瘤组织和正常组织标本,免疫组织化学法分析CCNA2表达水平,多因素分析其与临床病理特征的关系。基因富集分析(GSEA)评估结肠癌中CCNA2潜在分子功能。CIBERSORT算法计算CCNA2与结肠癌免疫细胞浸润的相关程度。结果数据库分析及免疫组织化学结果提示,CCNA2在结肠癌肿瘤组织中表达程度高于正常组织(P<0.001)。CCNA2高表达组的总体生存期、疾病特异生存期、无进展间隔期均长于低表达组(均P<0.05)。在肿瘤组织中,CCNA2的表达水平随病理分期及TNM分期的升高而降低(P<0.05)。正常组织的CCNA2表达程度均小于各个病理分期的肿瘤组织(均P<0.001)。GSEA提示,CCNA2低表达时有Wnt/β-Catenin、KRAS等信号通路富集。CIBERSORT分析显示,调节性T细胞和巨噬细胞M0等免疫细胞在CCNA2低表达时浸润增加。结论CCNA2在结肠癌中高表达,与病理分期、TNM分期密切相关,其可能通过KRAS、Wnt/β-Catenin通路募集调节性T细胞,减少免疫细胞浸润,促进结肠癌进展导致不良预后。Objective To investigate the relationship between cyclin A2(CCNA2)and the prognosis of colon cancer,and its possible mechanism from the perspective of immune infiltration.Methods We downloaded the transcriptome data of colon cancer patients from The Cancer Genome Atlas database.Clinicopathological feature analysis and survival analysis were performed based on the expression levels of CCNA2.A total of 75 specimens of colon cancer and normal tissues were collected,and the expression level of CCNA2 was analyzed using immunohistochemical methods.Multivariate analysis was conducted to explore its relationship with clinicopathological features.Gene Set Enrichment Analysis(GSEA)was used to assess the potential molecular functions of CCNA2 in colon cancer.CIBERSORT algorithm was applied to calculate the correlation between CCNA2 and immune-cell infiltration in colon cancer.Results Database and immunohistochemical analyses indicated that CCNA2 was expressed at a significantly higher level in colon cancer tissues than normal tissues(P<0.001).The overall survival,disease-specific survival,and progression-free interval were all longer in the group with high CCNA2 expression than the group with low expression(all P<0.05).In tumor tissues,the expression level of CCNA2 decreased with increased pathological and TNM stages(P<0.05).The expression level of CCNA2 in normal tissues was consistently lower than that in colon cancer tissues across all clinical stages(all P<0.001).GSEA suggested that Wnt/β-catenin,KRAS,and other signaling pathways were enriched when CCNA2 was lowly expressed.CIBERSORT analysis revealed an increase in the infiltration of immune cells such as regulatory T cells and macrophages M0 when CCNA2 expression was low.Conclusion CCNA2 is highly expressed in colon cancer and closely associated with grade of pathology and TNM stage.It may recruit regulatory T cells through the KRAS and Wnt/β-catenin pathways,thereby reducing immune-cell infiltration and promoting colon cancer progression,leading to poor prognosis.

关 键 词：CCNA2 结肠癌 肿瘤微环境 免疫浸润 预后 临床特征 生物信息学分析 

分 类 号：R735.35[医药卫生—肿瘤]