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