CXCR4 Negatively Correlates with NKT Cell Infiltration During Gastric Precancerous Lesions Progression to Early Gastric Cancer

Background Immune microenvironment in gastric precancerous lesions (GPL) and early gastric cancer (EGC) still remain largely unknown. This study aims to identify key immune cells and hub genes associated with GPL progression to EGC. Methods Immune Cell Abundance Identifier (ImmuCellAI) algorithm was used to quantify the proportions of immune cells of GPL and GC samples based on gene expression profiles. Key immune cells associated with GPL progression to EGC were identified using one‐way analysis of variance (ANOVA) test and Spearman’s correlation test. Weighted gene co-expression analysis (WGCNA) and pathway enrichment were adopted to identify hub gene co-expression network and hub genes associated with the key immune cells infiltration. The pattern of key immune cells infiltration, hub genes expression and their correlation were verified in an independent GPL-EGC cohort and GC datasets.Results NKT cell was found gradually decreased during GPL progression to EGC and negatively correlated with tumorigenesis. According to WGCNA and hub genes screening, CXCR4, having a poor prognosis, increased with GPL progression, positively correlated with tumorigenesis and negatively correlated with NKT cell infiltration significantly, was identified as the real hub gene. The negative correlation between CXCR4 and NKT cell infiltration was successfully verified in an independent GPL-EGC cohort and GC datasets.Conclusion CXCR4 and NKT cell are possible to serve as biomarkers in monitoring GPL progression to EGC. Besides, CXCR4 may be involved in regulating NKT cell infiltration during GPL progression to EGC, which may provide a new immunotherapeutic target.