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Pei-Ming Zheng, Li-Bo Ouyang, Rong Wang, Ke-Ying Jing, Chun-Kai Zhu, Department of Clinical Laboratory, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
Hui-Jie Gao, Department of Oncology, The First Affiliated Hospital of Henan University, Kaifeng 475000, Henan Province, China
Co-first authors: Pei-Ming Zheng and Li-Bo Ouyang.
Author contributions: Zheng PM conducted the majority of experiments and wrote the manuscript; Zheng PM, Ouyang LB and Wang R designed the study and served as a scientific advisor and guarantor; Wang R corrected the manuscript; Jing KY was involved in applying the analytical tools; Gao HJ and Zhu CK participated in the collection of human material.
Supported by the Henan Provincial Program for Young and Middle-Aged Innovators in Health Science and Technology, No. LJRC2024002; and the Natural Science Foundation of Henan Province, No. 252300421373.
Institutional review board statement: The study protocol was approved by the Henan Provincial People’s Hospital (approval No. 2023-126).
Informed consent statement: Informed consent was obtained from all study participants.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
Received: December 18, 2025 Revised: January 13, 2026 Accepted: February 4, 2026 Published online: May 7, 2026 Processing time: 127 Days and 20.1 Hours
Abstract
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.
Core Tip: Antinuclear antibody (ANA), extractable nuclear antigen (ENA) and systemic inflammation have been implicated in cancer prognosis, their combined role predicting outcomes of gastric cancer patients undergoing immunotherapy. This study confirmed autoantibody, particularly ANA/ENA, along with other indicators serves as independent factors for prognosis in gastric cancer patients undergoing immunotherapy. The assessment of autoantibody profiles provides a novel perspective for optimizing risk stratification and treatment methods.
