Clinical prognosis evaluation of alpha-fetoprotein-positive gastric cancer: comprehensive analysis and development of a novel nomogram for survival prediction

Abstract

Background: Alpha-fetoprotein (AFP) is an established biomarker for liver cancer, but its role in gastric cancer (GC) remains unclear. This study evaluated AFP's prognostic value in GC and developed a survival prediction model incorporating AFP and other clinical factors.

Methods: We analyzed 766 GC patients from Changzhou Traditional Chinese Medicine Hospital, categorizing them as AFP-positive (>20 ng/mL) or AFP-negative (≤20 ng/mL). Kaplan-Meier and Cox regression analyses assessed the association between AFP levels and overall survival (OS). A nomogram based on identified prognostic factors was created and evaluated using ROC curves, calibration curves, and decision curve analysis (DCA).

Results: Among 766 gastric cancer (GC) patients, 3.3% (n=25) exhibited elevated AFP levels (>20 ng/mL). The AFP-positive group demonstrated significantly more aggressive clinicopathological features, including larger tumor size (p < 0.05), deeper invasion (higher T-stage), increased lymph node metastasis (higher N-stage), and higher rates of distant metastasis (p = 0.035). Survival analysis revealed markedly worse outcomes for AFP-positive patients (Log-rank P < 0.001), with a 68% higher mortality risk (unadjusted HR =1.68, 95% CI: 1.27-2.23). Multivariate Cox regression confirmed AFP positivity as an independent prognostic factor (adjusted HR = 1.8, 95% CI: 1.03-3.14, p =0.04), alongside T4-stage, N3-stage, and distant metastasis. A prognostic nomogram integrating AFP levels and TNM staging achieved superior predictive accuracy (AUCs: 0.80-0.84) compared to TNM staging alone (AUCs: 0.70-0.74) across 1-, 3-, and 5-year survival. Calibration and decision curve analyses further validated the model's clinical utility, supporting its role in risk stratification and treatment planning.

Conclusions: AFP is a significant independent prognostic factor in gastric cancer, and its inclusion in a multivariate model enhances survival prediction. The prognostic nomogram developed in this study offers clinicians a valuable tool for predicting patient outcomes and guiding treatment decisions. Further validation and prospective studies are necessary to confirm the model's clinical applicability.

Keywords: alpha-fetoprotein; gastric cancer; metastasis; nomogram; prognosis.

Figure 1

Comparison of OS rates between AFP-positive GC and AFP-negative GC (P < 0.001).

Figure 2

Prognostic nomogram for predicting 1-, 3-, and 5-year overall survival in gastric cancer patients.

Figure 3

ROC curves comparing the nomogram and TNM staging system for predicting survival in gastric cancer. Nomogram performance (yellow lines: training cohort; blue lines: validation cohort) for 1-year (A), 3-year (C), and 5-year (E) survival. TNM staging performance (yellow lines: training cohort; blue lines: validation cohort) for 1-year (B), 3-year (D), and 5-year (F) survival.

Figure 4

Calibration curves assessing the agreement between nomogram-predicted and observed survival probabilities. (A) 1-year survival; (B) 3-year survival; (C) 5-year survival.

Figure 5

Decision curve analysis (DCA) evaluating the clinical utility of the nomogram across threshold probabilities. The nomogram (blue line) demonstrates significantly higher net benefit compared to the TNM staging system (yellow line) and the 'treat-all' (red lines) or 'treat-none' strategies (green lines).