# DKK3 and SERPINB5 as novel serum biomarkers for gastric cancer: facilitating the development of risk prediction models for gastric cancer

**Authors:** Yan-Yu Liu, Yan-Fang Fu, Wan-Yu Yang, Zheng Li, Qian Lu, Xin Su, Jin Shi, Si-Qi Wu, Di Liang, Yu-Tong He

PMC · DOI: 10.3389/fonc.2025.1536491 · Frontiers in Oncology · 2025-03-31

## TL;DR

This study identifies DKK3 and SERPINB5 as new blood markers for gastric cancer and uses them to build a highly accurate risk prediction model for early detection.

## Contribution

The study introduces DKK3 and SERPINB5 as novel serum biomarkers for gastric cancer and develops a high-accuracy risk prediction model.

## Key findings

- DKK3 levels were significantly decreased in gastric cancer patients (P<0.001).
- SERPINB5 levels were significantly elevated in gastric cancer patients (P<0.001).
- The risk prediction model achieved an AUC of 0.938, indicating high accuracy.

## Abstract

The existing gastric cancer (GC) risk prediction models based on biomarkers are limited. This study aims to identify new promising biomarkers for GC to develop a risk prediction model for effective assessment, screening, and early diagnosis. This study was conducted utilizing a large combined cohort for upper gastrointestinal cancer that was established in Hebei Province, China. General macro risk factors, Helicobacter pylori (H.pylori) infection status, and protein biomarkers were collected through questionnaire surveys and laboratory tests. Novel GC biomarkers were explored using data-independent acquisition (DIA) proteomics and enzyme-linked immunosorbent assay (ELISA). Multiple machine learning algorithms were used to identify key predictors for the GC risk prediction model, which was validated with an independent external cohort from multiple hospitals. A total of 530 participants aged 40 to 74 were analyzed, with 104 ultimately diagnosed with GC. Significant biomarkers in GC patients were identified by DIA combined ELISA, including elevated Keratin 7 (KRT7) and Mammary fibrostatin (SERPINB5) (P<0.001) and decreased Dickkopf-associated protein 3 (DKK3) (P<0.001). Factors such as sex, age, smoking status, alcohol consumption, family history of GC, H. pylori infection, DKK3 and SERPINB5 were used to create a multidimensional risk prediction model for GC. This model achieved an area under the curve (AUC) of 0.938 (95% confidence interval: 0.913-0.962). The risk prediction model developed in this study shows high accuracy and practical utility, serving as an effective preliminary screening tool for identifying high-risk individuals for GC.

## Linked entities

- **Genes:** DKK3 (dickkopf Wnt signaling pathway inhibitor 3) [NCBI Gene 27122], SERPINB5 (serpin family B member 5) [NCBI Gene 5268], KRT7 (keratin 7) [NCBI Gene 3855]
- **Diseases:** gastric cancer (MONDO:0001056)

## Full-text entities

- **Genes:** KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, DKK3 (dickkopf Wnt signaling pathway inhibitor 3) [NCBI Gene 27122] {aka CRRL, REIC, RIG}, SERPINB5 (serpin family B member 5) [NCBI Gene 5268] {aka PI5, maspin}
- **Diseases:** upper gastrointestinal cancer (MESH:D005770), H. pylori infection (MESH:D016481), GC (MESH:D013274)
- **Chemicals:** alcohol (MESH:D000438)
- **Species:** Helicobacter pylori (species) [taxon 210], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11994446/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC11994446/full.md

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Source: https://tomesphere.com/paper/PMC11994446