NLRP3 inflammasome expression affects immune cell infiltration and clinical prognosis in <em>Helicobacter pylori</em> infection‑associated gastric cancer

Wan,Chuandan; Xu,Yeqiong; Zhu,Yanping; Cao,Xuexian; Wang,Ping; Gu,Yulan

doi:10.3892/mmr.2025.13550

NLRP3 inflammasome expression affects immune cell infiltration and clinical prognosis in Helicobacter pylori infection‑associated gastric cancer

Authors:
- Chuandan Wan
- Yeqiong Xu
- Yanping Zhu
- Xuexian Cao
- Ping Wang
- Yulan Gu
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Affiliations: Central Laboratory, Changshu Medical Examination Institute, Changshu, Jiangsu 215500, P.R. China, Department of Oncology and Radiotherapy, Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu 215500, P.R. China, School of Basic Medical Sciences, Wannan Medical College, Wuhu, Anhui 241002, P.R. China
Published online on: April 28, 2025 https://doi.org/10.3892/mmr.2025.13550
Article Number: 185
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

High Helicobacter pylori infection rates contribute to high gastric cancer (GC) incidence. While H. pylori infection is associated with GC development its mechanisms are still being studied. The aim of the present study was to examine the differences between H. pylori infection‑induced GC and non‑infected tissues, and to investigate the correlation between nucleotide‑binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome expression and immune cell infiltration in GC, thus providing a theoretical basis for clinical prognosis and immunotherapy. High‑throughput RNA‑sequencing expression data from The Cancer Genome Atlas (TCGA) were analyzed. Additionally, TIMER2.0 and Kaplan‑Meier Plotter were used to analyze the differential expression of NLRP3 mRNA in various tumors, the effect of H. pylori infection on gene expression, and the association between NLRP3 and clinical prognosis among patients with GC. Immunohistochemistry (IHC) was used to assess the effects of NLRP3 protein expression on immune cell infiltration in clinical tissues with or without H. pylori infection. R software was used for data visualization and statistical analysis. TCGA data revealed that the expression levels of NLRP3 in GC tissues were increased compared with those in normal tissues (P<0.05), which was further validated in clinical samples. Furthermore, NLRP3 mRNA expression was significantly elevated in clinical GC tissues infected with H. pylori. Notably higher relative levels of NLRP3 mRNA were observed in tumor tissues with a tumor size ≥5 cm, lymph node metastasis, Tumor‑Node‑Metastasis stage III + IV or poor differentiation compared with the respective controls (P<0.05). IHC confirmed a significant increase in NLRP3 expression within H. pylori‑infected GC tissues compared with that in non‑infected tissues. In GC immune infiltration, NLRP3 expression was revealed to be associated with natural killer cell, whereas it was negatively correlated with regulatory T cells and CD8⁺ T cells. These findings indicated that NLRP3 may promote the polarization of tumor‑associated macrophages towards the M2 phenotype. High NLRP3 expression also promoted the infiltration of CD3⁺ and CD206⁺ cells, which significantly affected the survival rate of patients with GC. The immune infiltration of regulatory T lymphocytes was associated with better survival benefits for patients with GC; however, M2 macrophage infiltration was not conducive to the survival of patients with GC. Furthermore, survival analysis showed that high expression of NLRP3 was associated with a poorer 5‑year overall survival, progression‑free survival and post‑progression survival rates. In conclusion, elevated NLRP3 expression, which may be induced by H. pylori infection, could promote immune cell infiltration potentially by regulating cancer cell proliferation and migration, ultimately leading to an unfavorable prognosis and a notable reduction in the 5‑year survival rate.

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