Science Bite (3 minute oral presentation with PPT in live session and poster) - Students, ECRs and EMCRs only 16th Lorne Infection and Immunity 2026

Loss of expression of the tumour surveillance protein NLRC5 in chief cells undergoing transdifferentiation in Helicobacter pylori-associated carcinogenesis (131118)

Xiaohu Zhao 1 2 , Peinan Zhao 3 , Chengpeng Sun 4 , Nina Colon 1 , Angus Cramond 1 2 , Xingzong Huang 5 , Le Ying 1 2 6 , Ting Yang 5 , Yan Wang 4 , Dongmei Tong 1 2 , Richard L. Ferrero 1 2 7
  1. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia
  2. Department of Molecular and Translational Science, Monash University, Clayton, VIC, Australia
  3. Bioinformatics and Computational Biology, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
  4. Department of Pathology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
  5. Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
  6. Department of Medicine, Monash University, Melbourne, VIC, Australia
  7. Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, VIC, Australia

Background: NOD-like receptor family CARD domain-containing protein 5 (NLRC5) plays a key role in immune surveillance. It was shown that low levels of NLRC5 expression correlated with poor prognosis for many solid tumours. The role of NLRC5 in gastric carcinogenesis, however, was not investigated. From Kaplan-Meier plots, we found that high NLRC5 expression was associated with improved survival in gastric cancer (p = 0.0053). The aims of this study were to investigate NLRC5 expression in the gastric epithelium and its association with Helicobacter pylori-induced pathology.

Methods: To address the study aims, we analysed NLRC5 expression in publicly available single-cell RNA sequencing (scRNA-seq) datasets from cases of gastritis (GS), intestinal metaplasia (IM) and gastric cancer (GC) (GSE249874). Immunohistochemistry (IHC) and immunofluorescence (IF) were performed on human and mouse gastric biopsies to evaluate NLRC5-positivity and localisation.

Results: NLRC5 expression was detected in epithelial, immune and endothelial cells from GS, IM, and GC tissues. Its expression was significantly upregulated in H. pylori-positive gastritis (Wilcoxon, p<2.2e-16), particularly in chief cells located at the gastric gland base, but not in surface pit cells (verified by IHC and IF in human gastric samples). As gastric carcinogenesis progressed, however, expression declined in parallel with the loss of chief cells and transdifferentiation into spasmolytic polypeptide-expressing metaplasia (SPEM), a proposed precursor of gastric cancer.

Conclusion: NLRC5/NLRC5 expression in response to H. pylori infection appears to be localised specifically to chief cells at the gland base rather than the surface epithelial cells. Preliminary findings suggest that chief cell-derived NLRC5 may be involved in modulating gastric epithelial responses during H. pylori-associated carcinogenesis. A reduction in NLRC5 expression may potentially facilitate the transdifferentiation of chief cells into SPEM lineages, thereby contributing to metaplastic progression and tumour development.