# NKAIN1 expression relates to the immune evasion and prognosis of gastric cancer

**Authors:** Lindong Zhou, Yinfei Cheng, Peng Liu, Xiaoxia Jin, Qiang Xu, Xiaoxiang Li

PMC · DOI: 10.1038/s41598-025-30676-0 · Scientific Reports · 2025-12-06

## TL;DR

This study finds that higher NKAIN1 levels in gastric cancer are linked to immune evasion and worse patient outcomes, suggesting it could be a new target for treatment.

## Contribution

The study identifies NKAIN1 as a novel prognostic marker and potential therapeutic target in gastric cancer.

## Key findings

- NKAIN1 expression is significantly higher in gastric carcinoma tissues compared to non-tumor tissues.
- NKAIN1 expression correlates with immune checkpoint markers CTLA-4 and PD-L1 in gastric cancer.
- Increased NKAIN1 protein expression is an independent predictor of poor clinical outcomes in gastric cancer.

## Abstract

Patients with gastric cancer often exhibit poor responses to immunotherapy and experience unfavorable outcomes. This study aims to investigate the relationship between NKAIN1 levels in the tumor microenvironment and gastric carcinoma patients characteristics. Gene expression analysis, multiplex immunohistochemistry using tissue microarrays, and Quantitative Pathology Imaging System were conducted for determining the expression of NKAIN1 in gastric carcinoma tissues and association with patient outcomes. Additionally, we used the Spearman correlation method to assess the relationship between NKAIN1 protein expression in the tumor immune microenvironment and immune checkpoint markers of gastric carcinoma. Lastly, we evaluated the predictive significance of NKAIN1 presence using Cox regression models. The study findings indicated a significant increase in NKAIN1 expression in gastric carcinoma tissues compared to non-tumor stomach tissues. Moreover, a clear association between NKAIN1 expression and CTLA-4, as well as PD-L1, was identified. Importantly, the increased NKAIN1 protein expression was identified as an independent prognostic factor for adverse clinical outcomes in gastric cancer. In conclusion, this study supports NKAIN1 as a prognostic marker and promising target for immune therapy in stomach carcinoma.

The online version contains supplementary material available at 10.1038/s41598-025-30676-0.

## Linked entities

- **Genes:** NKAIN1 (sodium/potassium transporting ATPase interacting 1) [NCBI Gene 79570], CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493], CD274 (CD274 molecule) [NCBI Gene 29126]
- **Diseases:** gastric cancer (MONDO:0001056), gastric carcinoma (MONDO:0004950)

## Full-text entities

- **Genes:** NKAIN1 (sodium/potassium transporting ATPase interacting 1) [NCBI Gene 79570] {aka FAM77C}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}
- **Diseases:** gastric cancer (MESH:D013274), tumor (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12783303/full.md

## References

6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12783303/full.md

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Source: https://tomesphere.com/paper/PMC12783303