铁死亡基因NCOA4的表达水平与结肠癌预后和疗效的关系研究

doi:10.19586/j.2095-2341.2025.0038

生物技术进展 ›› 2026, Vol. 16 ›› Issue (1): 178-189.DOI: 10.19586/j.2095-2341.2025.0038

铁死亡基因NCOA4的表达水平与结肠癌预后和疗效的关系研究

刘晓霖(), 王琪慧()

武汉大学中南医院，武汉 430071

收稿日期:2025-03-20 接受日期:2025-10-11 出版日期:2026-01-25 发布日期:2026-02-12
通讯作者: 王琪慧
作者简介:刘晓霖 E-mail:Liuxl2795@163.com；

The Relationship Between the Expression Level of Ferroptosis-related Gene NCOA4 and Prognosis and Therapeutic Efficacy in Colon Cancer

Xiaolin LIU(), Qihui WANG()

Zhongnan Hospital of Wuhan University，Wuhan 430071，China

Received:2025-03-20 Accepted:2025-10-11 Online:2026-01-25 Published:2026-02-12
Contact: Qihui WANG

摘要/Abstract

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

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

中图分类号:

Q279

刘晓霖, 王琪慧. 铁死亡基因NCOA4的表达水平与结肠癌预后和疗效的关系研究[J]. 生物技术进展, 2026, 16(1): 178-189.

Xiaolin LIU, Qihui WANG. The Relationship Between the Expression Level of Ferroptosis-related Gene NCOA4 and Prognosis and Therapeutic Efficacy in Colon Cancer[J]. Current Biotechnology, 2026, 16(1): 178-189.

图/表 7

表1 NCOA4表达与患者临床症状的关系

Table 1 Relationship between NCOA4 expression and clinical characteristics of patients

特征	分类标准	NCOA4低表达组	NCOA4高表达组	P值
样本数量	n	239	239
性别，n（%）	女	120(25.1%)	106(22.2%)	0.234^‡
性别，n（%）	男	119(24.9%)	133(27.8%)	0.234^‡
年龄，n（%）	≤65	98(20.5%)	96(20.1%)	0.926^‡
年龄，n（%）	>65	141(29.5%)	143(29.9%)	0.926^‡
种族，n（%）	亚洲人	5(1.6%)	6(2.0%)	0.68^▷
	黑人或非裔美国人	37(12.1%)	26(8.5%)
	白种人	127(41.5%)	105(34.3%)
病理分期，n（%）	Ⅰ期	39(8.4%)	42(9.0%)	0.162^‡
	Ⅱ期	84(18.0%)	103(22.1%)
	Ⅲ期	72(15.4%)	61(13.1%)
	Ⅳ期	39(8.4%)	27(5.8%)
T期，n（%）	T1期	5(1.0%)	6(1.3%)	0.946^‡
	T2期	41(8.6%)	42(8.8%)
	T3期	161(33.8%)	162(34.0%)
	T4期	32(6.7%)	28(5.9%)
N期，n（%）	N0期	133(27.8%)	151(31.6%)	0.169^‡
	N1期	62(13.0%)	46(9.6%)
	N2期	44(9.2%)	42(8.8%)
M期e，n（%）	M0期	163(39.3%)	186(44.8%)	0.087^‡
M期e，n（%）	M1期	39(9.4%)	27(6.5%)	0.087^‡
年龄，中位数（IQR）		69(58,76.5)	69(59,78)	0.553^§

图1 结肠癌中NCOA4的表达分析A：NCOA4在泛癌组织中的表达水平。肿瘤：表示癌症患者的肿瘤样本，正常：表示癌症患者的正常癌旁组织，白色背景区域表示缺乏正常对照的肿瘤组织； B：NCOA4在正常组织和结肠癌中的表达水平；C：NCOA4在正常组织和结肠癌配对样本中的表达水平；D：NCOA4在不同年龄中的表达水平；E：NCOA4在不同性别中的表达水平；F：NCOA4在不同T期中的表达水平；G：NCOA4在不同M期中的表达水平；H：NCOA4在不同N期中的表达水平；I：NCOA4在不同病理分期中的表达水平；J：NCOA4在不同年龄亚组中的表达水平；K：NCOA4在不同分期亚组中的表达水平

Fig. 1 Expression analysis of NCOA4 in colorectal cancer

图2 结肠癌中NCOA4的预后价值A：NCOA4表达预测结肠癌的ROC曲线；B：NCOA4在结肠癌中的生存分析；C：NCOA4及其他临床病理症状与结肠癌患者OS的单因素及多因素回归分析；D：预测结肠癌患者1年、3年、5年OS的Nomogram列线图；E：预测结肠癌患者1年、3年、5年OS的Calibration矫正曲线

Fig. 2 Prognostic value of NCOA4 in colorectal cancer

图3 NCOA4的共表达基因和差异基因分析A：Top50差异基因的表达热图，蓝色表示低表达，红色表示高表达；B：NCOA4及其共表达系数最大的前11个基因的共表达热图；C：GO富集分析；D：KEGG富集分析；E：在NCOA4高低表达组差异基因的GSEA分析

Fig. 3 Co-expression gene and differentially expression genes analysis of NCOA4

图4 NCOA4表达与免疫浸润相关的分析A：NCOA4表达与肿瘤浸润免疫细胞的关联；B：基于ESTIMATE算法分析NCOA4表达与基质打分和免疫打分的关联；C：22个免疫细胞与NCOA4表达的相关性棒棒糖图；D：NCOA4表达和TMB的相关性散点图；E：29个免疫检查点与NCOA4表达的相关性热图矩阵

Fig. 4 Analysis of NCOA4 expression and immune infiltration

图5 NCOA4高、低表达组化疗药物的敏感性分析A~D：基于AZ628、LAQ824、紫杉醇、舒尼替尼对结肠癌患者的IC50值，评价NCOA4高、低表达组化疗药物的敏感性；E~H：NCOA4高、低表达组抗CTLA-4抗体和PD-1/PD-L1抗体应答的相对概率

Fig. 5 Drug sensitivity analysis of chemotherapy drugs in high and low NCOA4 expression groups

图6 人类蛋白质图谱（HPA）中NCOA4蛋白在正常结肠组织和结肠癌患者结肠组织中的表达A：正常结肠组织；B: 结肠癌患者的结肠组织。Antibody HPA065208，10×

Fig. 6 Expression of NCOA4 protein in human proteome map (HPA) in normal colon tissue and colon tissue of colorectal cancer patients

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铁死亡基因NCOA4的表达水平与结肠癌预后和疗效的关系研究

The Relationship Between the Expression Level of Ferroptosis-related Gene NCOA4 and Prognosis and Therapeutic Efficacy in Colon Cancer

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