Discovery and preliminary validation of five early gastric cancer biomarkers, including TAGLN2 and CTSD, based on serum proteomics

Background and purpose: Gastric cancer, as one of the most common malignant tumors, requires early diagnosis and treatment to improve patient prognosis. This study, based on serum quantitative proteomics research of early-stage gastric cancer patients and non-gastric cancer patients, aims to identif...

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Main Author: DU Kewei, ZHANG Shangdi, HU Wenfei, GAO Shan, GAN Jianxin, YOU Chongge
Format: Article
Language:English
Published: Editorial Office of China Oncology 2025-06-01
Series:Zhongguo aizheng zazhi
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Online Access:https://www.china-oncology.com/fileup/1007-3639/PDF/1752457540937-1134545099.pdf
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Summary:Background and purpose: Gastric cancer, as one of the most common malignant tumors, requires early diagnosis and treatment to improve patient prognosis. This study, based on serum quantitative proteomics research of early-stage gastric cancer patients and non-gastric cancer patients, aims to identify potential diagnostic biomarkers for early gastric cancer. Methods: Serum samples from primary gastric cancer patients and healthy control individuals were collected from Lanzhou University Second Hospital between June and December 2023, following inclusion and exclusion criteria. A protein spectral library was established using Data-Dependent Acquisition (DDA) mode, and each sample was analyzed using Data-Independent Acquisition (DIA) mode. The STRING database was used to analyze protein-protein interactions of upregulated proteins in gastric cancer serum. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used to analyze the pathways and functional annotations of the corresponding genes. Gene expression levels in gastric cancer and non-gastric cancer tissues were analyzed using GEPIA 2, and overall survival of each gene in gastric cancer was analyzed using Kaplan-Meier Plotter. Differential gene expression in clinical gastric cancer and adjacent tissues was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) This study was approved by the Ethics Committee of Lanzhou University Second Hospital (Ethical No.: 2023A-459) and was exempt from the informed consent. Results: Finally, serum samples from 30 primary gastric cancer patients, 29 healthy control individuals, along with the para-cancerous tissues from 8 patients were collected. A total of 666 intersecting proteins were identified through serum quantitative proteomics. Among them, 16 proteins showed upregulated expression and 22 proteins showed downregulated expression in the gastric cancer group (P<0.05, |FC|≥1.5). STRING database analysis showed that 10 upregulated proteins were involved in interaction networks. KEGG and GO analysis indicated that these genes were closely related to the biological processes of cancer occurrence and development. GEPIA 2 and Kaplan-Meier Plotter analysis showed that 6 genes, B2M, TAGLN2, CTSD, HSP90AB1, SH3BGRL3, and CFL1, which were highly expressed in the gastric cancer group (P<0.05) and associated with poor prognosis. Clinical verification by qRT-PCR confirmed that TAGLN2, CTSD, SH3BGRL3, CFL1 and HSP90AB1 were highly expressed in gastric cancer tissues (P<0.05). Conclusion: TAGLN2, CTSD, SH3BGRL3, CFL1, and HSP90AB1 have the potential to serve as clinical early gastric cancer diagnostic serum biomarkers, which may facilitate early diagnosis and treatment of gastric cancer.
ISSN:1007-3639