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Promising protein biomarkers for early gastric cancer: clinical performance of combined detection

  • Weifeng Shen , Hui Zhou , Lanqing Li , Wei Liu , Qinqin Lou , Claire Y. Tong , Junshun Gao , Junli Gao EMAIL logo and Pingyang Shao EMAIL logo
Published/Copyright: May 1, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 9

Abstract

Objectives

In the early stage of gastric cancer (GC), identifying cancer-specific biomarkers is a key step in the disease screening process. This study aims to explore the clinical value of five novel protein biomarkers and their combination (5 MP) for GC early diagnosis.

Methods

The candidate biomarkers were mined from TCGA, GTEx, and CPTAC databases. The clinical value of the five biomarkers and 5 MP in the early diagnosis from healthy control, benign gastric disease (BGD), precancerous lesions (PLGC), early GC (EGC), and GC was evaluated by receiver operator characteristic curve (ROC), the area under the curve (AUC), sensitivity, specificity, and accuracy.

Results

Five candidate biomarkers, COL10A1, GKN1, GKN2, LIPF, and REG4, were mined from TCGA, GTEx, and CPTAC databases. In the training cohort, the five proteins were confirmed to be differentially expressed in the serum of control, BGD, EGC, and GC. COL10A1 has the highest AUC of a single protein in control vs. EGC (0.857). GKN2 has the highest AUC of a single protein in BGD vs. EGC (0.822). 5 MP has an AUC of 0.890 in Control vs. EGC, and 0.854 in BGD vs. EGC. In the validation cohort, 5 MP has an AUC of 0.834 in PLGC vs. GC, and 0.839 in PLGC vs. EGC.

Conclusions

Our findings suggest that COL10A1, GKN1, GKN2, LIPF, and REG4 are useful non-invasive serum biomarkers for GC diagnosis. Combination detection (5 MP) has enhanced early diagnosis of GC and distinguishing between benign and malignant gastric diseases.

Keywords: gastric cancer; protein biomarker; early diagnosis; benign and malignant gastric diseases
Corresponding authors: Junli Gao, Jiaxing Key Laboratory of Clinical Laboratory Diagnostics and Translational Research, Affiliated Hospital of Jiaxing University, Jiaxing, China; and Hangzhou Cosmos Wisdom Mass Spectrometry Center of Zhejiang University Medical School, Hangzhou 311200, China, E-mail: ; and Pingyang Shao, Department of Clinical Laboratory, Affiliated Hospital of Jiaxing University, Jiaxing 314000, China; and Jiaxing Key Laboratory of Clinical Laboratory Diagnostics and Translational Research, Affiliated Hospital of Jiaxing University, Jiaxing, China, E-mail:
Weifeng Shen and Hui Zhou contributed equally to this work.

Funding source: Basic Public Welfare Research Program of Zhejiang Province

Award Identifier / Grant number: LGF22H160018

Funding source: the Science and Technology Project of Jiaxing City

Award Identifier / Grant number: 2020AD30054

Funding source: Jiaxing Key Discipiline of Medcine -- Clinical diagnostics

Award Identifier / Grant number: 2023-ZC-002

Funding source: Medical and Health Science and Technology Program of Zhejiang Province

Award Identifier / Grant number: 2023KY331

Acknowledgments

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  1. Research ethics: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). All the procedures of this study have been approved by the Medical Ethics Committee of the First Hospital of Jiaxing (ethics number: LS2021-KY-028).

  2. Informed consent: All informed consent was obtained from the subject(s) and/or guardian(s).

  3. Author contributions: Shen, Weifeng: Conceptualization, Supervision, Writing – review & editing; Zhou, Hui: Data curation, Methodology, Validation; Li, Lanqing: Data curation, Visualization, Writing - original draft; Liu, Wei: Data curation, Methodology, Validation; Lou, Qinqin: Data curation, Visualization, Writing - original draft; Tong, Claire Y: Formal analysis, Investigation, Validation; Gao, Junshun: Project administration, Resources, Supervision; Gao, Junli: Project administration, Resources, Supervision; Shao, Pingyang: Project administration, Resources, Supervision.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: This study was supported by Basic Public Welfare Research Program of Zhejiang Province (LGF22H160018), Medical and Health Science and Technology Program of Zhejiang Province (2023KY331), the Science and Technology Project of Jiaxing City (2020AD30054), and Jiaxing Key Discipiline of Medcine -- Clinical diagnostics (2023-ZC-002).

  7. Data availability: The raw data can be obtained on request from the corresponding author.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-1510).

Received: 2024-08-22
Accepted: 2025-04-16
Published Online: 2025-05-01
Published in Print: 2025-08-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2024-1510
Keywords for this article
gastric cancer; protein biomarker; early diagnosis; benign and malignant gastric diseases

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Macroprolactinaemia – some progress but still an ongoing problem
  4. Review
  5. Understanding the circulating forms of cardiac troponin: insights for clinical practice
  6. Opinion Papers
  7. New insights in preanalytical quality
  8. IFCC recommendations for internal quality control practice: a missed opportunity
  9. Genetics and Molecular Diagnostics
  10. Evaluation of error detection and treatment recommendations in nucleic acid test reports using ChatGPT models
  11. General Clinical Chemistry and Laboratory Medicine
  12. Pre-analytical phase errors constitute the vast majority of errors in clinical laboratory testing
  13. Improving the efficiency of quality control in clinical laboratory with an integrated PBRTQC system based on patient risk
  14. IgA-type macroprolactin among 130 patients with macroprolactinemia
  15. Prevalence and re-evaluation of macroprolactinemia in hyperprolactinemic patients: a retrospective study in the Turkish population
  16. Defining dried blood spot diameter: implications for measurement and specimen rejection rates
  17. Screening primary aldosteronism by plasma aldosterone-to-angiotensin II ratio
  18. Assessment of serum free light chain measurements in a large Chinese chronic kidney disease cohort: a multicenter real-world study
  19. Beyond the Hydrashift assay: the utility of isoelectric focusing for therapeutic antibody and paraprotein detection
  20. Direct screening and quantification of monoclonal immunoglobulins in serum using MALDI-TOF mass spectrometry without antibody enrichment
  21. Effect of long-term frozen storage on stability of kappa free light chain index
  22. Impact of renal function impairment on kappa free light chain index
  23. Standardization challenges in antipsychotic drug monitoring: insights from a national survey in Chinese TDM practices
  24. Potential coeliac disease in children: a single-center experience
  25. Vitamin D metabolome in preterm infants: insights into postnatal metabolism
  26. Candidate Reference Measurement Procedures and Materials
  27. Development of commutable candidate certified reference materials from protein solutions: concept and application to human insulin
  28. Reference Values and Biological Variations
  29. Biological variation of serum cholinesterase activity in healthy subjects
  30. Hematology and Coagulation
  31. Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies
  32. Cancer Diagnostics
  33. Promising protein biomarkers for early gastric cancer: clinical performance of combined detection
  34. Infectious Diseases
  35. The accuracy of presepsin in diagnosing neonatal late-onset sepsis in critically ill neonates: a prospective study
  36. Corrigendum
  37. The Unholy Grail of cancer screening: or is it just about the Benjamins?
  38. Letters to the Editor
  39. Analytical validation of hemolysis detection on GEM Premier 7000
  40. Reconciling reference ranges and clinical decision limits: the case of thyroid stimulating hormone
  41. Contradictory definitions give rise to demands for a right to unambiguous definitions
  42. Biomarkers to measure the need and the effectiveness of therapeutic supplementation: a critical issue
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