Identification of Malassezia globosa as a Gastric Fungus Associated with PD-L1 Expression and Overall Survival of Patients with Gastric Cancer

Abstract

Background. Microbiotas affected the prognosis of cancer patients by regulating programmed death ligand-1 (PD-L1) expression. However, the relationship between gastric fungi and PD-L1 expression is still unclear in gastric cancer (GC). We aimed at exploring the association of gastric fungi with PD-L1 expression and overall survival in GC. Methods. A total of 61 GC patients were divided into the two groups based on the PD-L1 combined positive scores (CPS). Fungal profiling was performed by internal transcribed spacer rDNA sequencing, and the survival analyses were performed by Kaplan-Meier curves. Results. We observed a taxonomic difference of fungi between the PD-L1-High (CPS≥10) and PD-L1-Low group (CPS<10) by principal coordinates analysis (PCoA) (P=0.014 for Bray-Curtis and P=0.042 for Jaccard). Malassezia had a higher abundance in the PD-L1-High group compared to the PD-L1-Low group (P=0.045). Malassezia globosa elevated significantly in the PD-L1-High group. GC patients with PD-L1 low expression and low abundance of Malassezia globosa had a longer overall survival (OS) than others (P=0.047). Malassezia globosa was associated with PD-L1 expression (Odds Ratio=3.509, 95% Confidence Interval: 1.056-11.656, P=0.040). Malassezia globosa was associated with the tumor size (P=0.031) and PD-L1 status (P=0.024). GC patients with a high abundance of Malassezia globosa had shorter OS than others (P=0.028). Malassezia globosa was an independent factor (Hazard Ratio=3.080, 95% Confidence Interval: 1.140-8.323, P=0.027) for OS after adjusting for tumor stage. Malassezia globosa was figured out to be associated with- fatty acid and lipid biosynthesis and degradation via LIPASYN pathway. Conclusions. Malassezia globosa was identified as a PD-L1 expression-associated gastric fungus and associated with OS of GC patients, which calls for more studies to further explore its potential in PD-L1/PD-1 targeted immunotherapy.