天津医药

天津医药 ›› 2026, Vol. 54 ›› Issue (9): 934-940.doi: 10.11958/20253483

• 临床研究 • 上一篇    下一篇

基于NFE2L1、TRIM26表达构建并验证预测免疫治疗转移性胃癌患者生存期的列线图模型

张佳明1(), 班志超1,△(), 常黎明1, 周医斋2   

  1. 1 保定市第二中心医院消化内科（邮编072750）
    2 保定市第二中心医院骨科（邮编072750）
  • 收稿日期:2025-12-10 修回日期:2026-03-10 出版日期:2026-09-15 发布日期:2026-09-14
  • 通讯作者: △E-mail：bzczyz@163.com
  • 作者简介:张佳明（1993），男，主治医师，主要从事消化道肿瘤早诊早治方面研究。E-mail：15097773273@163.com
  • 基金资助:
    保定市科技计划项目(2541ZF016)

Development and validation of a nomogram model based on NFE2L1 and TRIM26 expression for predicting survival in metastatic gastric cancer patients receiving immunotherapy

ZHANG Jiaming1(), BAN Zhichao1,△(), CHANG Liming1, ZHOU Yizhai2   

  1. 1 Department of Gastroenterology, Baoding No.2 Central Hospital, Baoding 072750, China
    2 Department of Orthopedics, Baoding No.2 Central Hospital, Baoding 072750, China
  • Received:2025-12-10 Revised:2026-03-10 Published:2026-09-15 Online:2026-09-14
  • Contact: △E-mail：bzczyz@163.com

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摘要：

目的 基于核因子E2相关因子1（NFE2L1）与三重基序蛋白26（TRIM26）的表达，结合临床病理特征，构建并验证一种预测接受免疫治疗的转移性胃癌患者生存期的列线图模型。方法 选取于该院接受免疫治疗的转移性胃癌患者分别作为建模组（252例）和内部验证组（108例），并选取于外院接受治疗的62例患者作为外部验证组。收集患者的临床资料，免疫组织化学法检测NFE2L1和TRIM26表达，采用多因素Cox比例风险回归模型筛选独立预后因素，并构建列线图预测模型。采用受试者工作特征曲线计算曲线下面积（AUC）、一致性指数（C-index）、校准曲线（Hosmer-Lemeshow检验），临床决策曲线分析（DCA）评估模型的区分度、校准度及临床适用性。结果 建模组中，肿瘤浸润深度为T3—4期，肿瘤最大径≥5 cm，低、中分化者及NFE2L1、TRIM26高表达者的总生存期（OS）较相应参数组短（P<0.05）。多因素Cox回归分析显示，肿瘤浸润深度为T3—4期、肿瘤最大径≥5 cm以及NFE2L1和TRIM26高表达是转移性胃癌患者免疫治疗后OS较短的独立危险因素。基于上述4项因素构建的列线图模型在建模组中显示出良好的区分能力（1年生存率AUC=0.924，95%CI：0.849~0.969；2年生存率AUC=0.823，95%CI：0.787~0.902；C-index=0.887，95%CI：0.742~0.940），内部验证组（1年生存率AUC=0.896，95%CI：0.800~0.910；2年生存率AUC=0.860，95%CI：0.785~0.918；C-index=0.850，95%CI：0.733~0.919）与外部验证组（1年生存率AUC=0.864，95%CI：0.783~0.910；2年生存率AUC=0.830，95%CI：0.752~0.900；C-index=0.832，95%CI：0.715~0.908）亦验证了其良好的区分度。校准曲线显示，建模组（Hosmer-Lemeshow检验χ²=6.325，P=0.618）、内部验证组（χ²=7.152，P=0.523）及外部验证组（χ²=8.021，P=0.426）的预测概率与实际概率拟合良好。DCA显示，在0.10~0.90阈值概率范围内，模型净效益显著高于“全干预”和“不干预”方案，临床适用性强。结论 肿瘤浸润深度T3—4期、肿瘤最大径≥5 cm、NFE2L1及TRIM26高表达是转移性胃癌患者免疫治疗后OS较短的独立危险因素，基于上述指标构建的列线图模型可有效预测患者OS。

关键词: NF-E2相关因子1, TRIM26蛋白, 人, 免疫疗法, 胃肿瘤, 生存分析, 列线图

Abstract:

Objective To develop and validate a nomogram model integrating nuclear factor erythroid 2-related factor 1 (NFE2L1) and tripartite motif-containing protein 26 (TRIM26) expression levels for predicting survival in metastatic gastric cancer (mGC) patients undergoing immunotherapy. Methods A total of 252 mGC patients treated with immunotherapy at our hospital were selected as the training cohort. Through simple random sampling, 108 patients were allocated as the internal validation cohort, while 62 patients from external institutions were selected as the external validation cohort. Clinicopathological characteristics (gender, age, tumor invasion depth) were collected. The expressions of NFE2L1 and TRIM26 were detected by immunohistochemistry. Univariate and multivariate Cox proportional hazards regression models identified independent prognostic factors to construct the nomogram. Internal validation employed bootstrap resampling (1 000 iterations). Discriminative ability was assessed via area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration via Hosmer-Lemeshow test, and clinical utility via decision curve analysis (DCA). Results In the modeling group, the overall survival (OS) of those with tumor invasion depth of T3-4 stage, the maximum tumor diameter ≥5 cm, low and moderate differentiation and high expression of NFE2L1 and TRIM26 was shorter than those of the corresponding parameter groups (P<0.05). Multivariate Cox analysis demonstrated that tumor invasion depth (HR=1.565, 95%CI: 1.132-2.164), maximum tumor diameter (HR=1.428, 95%CI: 1.088-1.871), high NFE2L1 expression (HR=2.788, 95%CI: 1.926-3.995) and high TRIM26 expression (HR=2.451, 95%CI: 1.759-3.412) were independent risk factors for shorter survival following immunotherapy (all P<0.05). The nomogram exhibited excellent discriminative ability in the training cohort (1-year AUC=0.924, 95%CI: 0.849-0.969; 2-year AUC=0.823, 95%CI: 0.787-0.902; C-index=0.887, 95%CI: 0.742-0.940), internal validation cohort (1-year AUC=0.896, 95%CI: 0.800-0.910; 2-year AUC=0.860, 95%CI: 0.785-0.918; C-index=0.850, 95%CI: 0.733-0.919), and external validation cohort (1-year AUC=0.864, 95%CI: 0.783-0.910; 2-year AUC=0.830, 95%CI: 0.752-0.900; C-index=0.832, 95%CI: 0.715-0.908). Calibration curves confirmed good agreement between predicted and observed outcomes (training cohort: χ²=6.325, P=0.618; internal validation: χ²=7.152, P=0.523; external validation: χ²=8.021, P=0.426). Decision curve analysis revealed superior net clinical benefit across threshold probabilities of 0.10-0.90 compared to alternative strategies. Conclusion Tumor invasion depth at stage T3-4, maximum tumor diameter ≥5 cm and high expression of NFE2L1 and TRIM26 are independent risk factors for the OS of immunotherapy in patients with metastatic gastric cancer. The nomogram model constructed based on the above indicators can effectively predict the OS of patients.

Key words: NF-E2-related factor 1, TRIM26 protein, human, immunotherapy, stomach neoplasms, survival analysis, nomograms

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