Abstract
Purpose
Early diagnosis is crucial for optimal prognosis of gastric cancer (GC). Hereby, we aimed to identify novel serum autoantibody-based biomarkers for precancerous lesion (PL) and early GC.
Methods
We performed serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (Nano-LC-Q-TOF-MS/MS) to screen for GC-associated autoantibodies. The identified autoantibodies were analyzed for potential detection value for PL and GC by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves analysis was conducted to evaluate the accuracy of the biomarkers.
Results
We identified seven candidates, such as mRNA export factor (RAE1), Nucleophosmin 1 (NPM1), phosphoglycerate kinase 1 (PGK1), and ADP-ribosylation factor 4 (ARF4). Antibodies against all seven proteins were present at higher levels in sera from 242 patients (51 PL, 78 early GC, 113 advanced GC) compared with sera from 122 healthy individuals. RAE1-specific autoantibody discriminated best between patients at different GC stages, with area under the curve (AUC) values of 0.710, 0.745, and 0.804 for PL, early GC, and advanced GC, respectively. Two predictive models composed of gender, RAE1, PGK1, NPM1, and ARF4 autoantibodies (Model 2 for PL) and of age, gender, RAE1, PGK1, and NPM1 autoantibodies (Model 3 for early GC) had improved diagnostic efficiencies, with AUCs of 0.803 and 0.857, sensitivities of 66.7% and 75.6%, and specificities of 78.7% and 87.7%, respectively.
Conclusion
The identified serum tumor-associated autoantibodies (TAAbs) may have good potential for early detection of GC and PL.
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Data availability
All datasets presented in this study are included in the article/Supplementary Material.
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Acknowledgements
We thank the patients for providing their samples for this study. We acknowledge the Beijing Friendship Hospital, Capital Medical University, and the Cancer Hospital, Chinese Academy of Medical Sciences for sample collection. We thank Anne M. O’Rourke, PhD, from Liwen Bianji (Edanz) (http://www.liwenbianji.cn), for editing the English text of a draft of this manuscript.
Funding
This work was funded by Grants from the National Major Science and Technology Projects of China (No.2017ZX10201201) and the Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals (No. XXZ0103).
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JR, SZ, and JH contributed to the project design. CZ, JX, and YX participated in collecting samples and clinical analysis. QZ, PH, ZC, SQ, QO, HZ, and HT participated in the implementation of the experiments. QZ and PH contributed to drafting the manuscript. DZ, YL, and JH contributed to revising the manuscript critically. All authors read and approved the final manuscript.
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The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the Beijing Friendship Hospital/Capital Medical University (No.2018-P2-058-01) and Cancer Hospital/Chinese Academy of Medical Sciences (No.14-067/857).
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Zhu, Q., He, P., Zheng, C. et al. Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion. J Cancer Res Clin Oncol 149, 8369–8378 (2023). https://doi.org/10.1007/s00432-023-04732-z
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DOI: https://doi.org/10.1007/s00432-023-04732-z