LRRC25 Is a Potential Biomarker for Predicting Immunotherapy Response in Patients with Gastric Cancer.

[BACKGROUND] Leucine-rich repeat containing 25 (LRRC25) is distinguishingly expressed in different tumor types, but the relationship with immune cell infiltration in gastric cancer stills unclear. We analyzed LRRC25 expression using pan-cancer data from The Cancer Genome Atlas and gene data from Gene Expression Omnibus. The clinical significance was further evaluated using gastric cancer tissues derived from clinical trials (no. NCT04208347).

[METHOD] Through bioinformatics analysis of TCGA database and the UCSC Xena database, we found the correlation between LRRC15, gastric cancer, and immune cell infiltration. Further, multiplex immunohistochemistry/immunofluorescence (mIHC/IF), tissue microarray, and image acquisition and quantitative analysis confirmed our theory.

[RESULTS] It was discovered that LRRC25 was highly expressed in gastric cancer. Further analysis revealed that the expression of LRRC25 associated with gene sets implicated in immunity, including those in innate immunity, adaptive immunity, and chemokine signaling pathways. The result of (mIHC/IF) suggests a negative relevance between LRRC25 and response of anti-PD-1 treatment and reveals a trend of consistent change on LRRC25 + cells and CD16 expression. We also discovered that LRRC25 expression significantly associated with immune cell infiltration level. In particular, there is a relationship between LRRC25 and the phenotype and function of NK cells.

[CONCLUSION] High LRRC25 expression contributes to immunosuppressive microenvironment by influencing chemokine axis in gastric cancer. LRRC25 may serve as a clinically useful biomarker for predicting neoadjuvant immunotherapeutic response in patients with gastric cancer. LRRC25 can affect the phenotype and function of NK cells.