Clinical significance of autoantibody profiling and systemic inflammation in predicting outcomes of gastric cancer patients undergoing immunotherapy

BACKGROUND The identification of reliable biomarkers is crucial for predicting outcomes in gastric cancer patients receiving immunotherapy. While autoantibodies antinuclear antibody (ANA) and extractable nuclear antigen (ENA) and systemic inflammation have been implicated in cancer prognosis, their combined role in this context remains to be fully elucidated. AIM To evaluate the clinical significance of autoantibodies, alongside tumor markers and inflammatory indicators, in gastric cancer patients undergoing immunotherapy. METHODS A retrospective cohort of 230 gastric cancer patients undergoing immunotherapy (anti-programmed cell death 1/programmed cell death ligand 1 antibodies combined with chemotherapy) was enrolled. Comprehensive clinical data, including autoantibody status (ANA, ENA), systemic inflammatory indicators (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, pan-immune-inflammation value, systemic immune-inflammation index), and tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 199], were collected. Kaplan-Meier survival analysis and univariate/multivariate Cox regression analyses were employed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS). The nomogram was constructed and receiver operating characteristic (ROC) curves were analyzed the efficacy of the prognostic model. RESULTS The presence of autoantibodies was significantly associated with better survival outcomes. Patients positive for ENA exhibited significantly longer OS (P = 0.046), while patients positive for ANA, ENA, and the combined ANA/ENA criterion showed significantly longer time of PFS (all P < 0.05). Multivariate analysis confirmed that tumor node metastasis (TNM) stage [hazard ratio (HR) = 3.292, P = 0.002] and CEA level (HR = 1.022, P = 0.010) were independent risk predictive factors for OS. For PFS, multivariate analysis confirmed that TNM stage (HR = 3.022, P = 0.004) and ANA/ENA criterion (HR = 0.538, P < 0.001) were independent risk predictive factors for PFS. The ROC results showed that the TNM and ANA/ENA models had certain diagnostic efficacy for PFS of patients. CONCLUSION Autoantibody positivity, particularly ANA/ENA, along with traditional tumor markers serves as independent biomarkers for prognosis in gastric cancer patients undergoing immunotherapy. The assessment of autoantibody profiles provides a novel perspective for optimizing risk stratification and treatment methods.