Abstract:

As a ferroptosis gene， nuclear receptor coactivator 4 （NCOA4） protects cells by eliminating free iron and glutathione. To explore the value of NCOA4 in predicting the therapeutic efficacy of colon cancer， its expression in colon cancer was analyzed using data from The Cancer Genome Atlas （TCGA）， with the aim of investigating its associations with prognosis， the immune microenvironment， and treatment response. The results showed that NCOA4 expression was significantly lower in colon cancer tissues than in normal tissues （P<0.05）， and its low expression was correlated with shorter overall survival （P<0.05）. Differentially expressed genes between the high and low NCOA4 expression groups were mainly enriched in immune- and tumor-related pathways. Additionally， NCOA4 expression was associated with the immune microenvironment， immune cell infiltration， and immune checkpoints. Further analyses of drug sensitivity and immunotherapy response revealed that colon cancer patients with low NCOA4 expression may exhibit better therapeutic responses to cytotoxic T-lymphocyte-associated protein 4 （CTLA4）-targeted therapy and chemotherapeutic agents such as Raf kinase inhibitors. In conclusion， low NCOA4 expression is associated with poor prognosis and impaired immune cell infiltration in colon cancer. Combined immune checkpoint-targeted therapy and chemotherapy may effectively treat colon cancer patients with low NCOA4 expression.

Key words: NCOA4, colon cancer, immune cell infiltration, drug sensitivity analysis, immunotherapy

摘要：

作为一种铁死亡基因，核受体辅激活因子4（nuclear receptor coactivator 4，NCOA4）可通过消除游离铁和谷胱甘肽起到保护细胞的作用。为了了解NCOA4预测结肠癌的疗效，通过分析癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据中NCOA4在结肠癌中的表达，探究了其与预后、免疫微环境及治疗的关系。研究结果显示，NCOA4在结肠癌组织中的表达低于正常组织（P<0.05），且其低表达与较短总生存期相关（P<0.05）。高、低NCOA4表达组间的差异基因主要富集于免疫及肿瘤相关通路。另外，NCOA4表达与免疫微环境、免疫细胞浸润及免疫检查点相关。进一步的药物敏感性与免疫治疗分析显示，NCOA4低表达的结肠癌患者对细胞毒性T淋巴细胞相关蛋白4（cytotoxic T lymphocyte antigen 4，CTLA4）靶向治疗以及Raf激酶抑制剂等化疗药物可能具有更好的治疗反应。综上，NCOA4低表达与结肠癌不良预后及免疫细胞浸润受损有关，针对免疫检查点靶向治疗并联合化疗药物可有效治疗NCOA4低表达的结肠癌患者。

关键词: NCOA4, 结肠癌, 免疫细胞浸润, 药物敏感性分析, 免疫治疗