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

Abstract

We observed a taxonomic difference of fungi between the PD-L1-High (<i>CPS</i> ≥ 10) and PD-L1-Low group (<i>CPS</i> < 10) by principal coordinates analysis (PCoA) (<i>P</i> = 0.014 for Bray-Curtis and <i>P</i> = 0.042 for Jaccard). <i>Malassezia</i> had a higher abundance in the PD-L1-High group compared to the PD-L1-Low group (<i>P</i> = 0.045). <i>Malassezia globosa</i> elevated significantly in the PD-L1-High group. GC patients with PD-L1 low expression and low abundance of <i>Malassezia globosa</i> had a longer overall survival (OS) than others (<i>P</i> = 0.047). <i>Malassezia globosa</i> was associated with PD-L1 expression (<i>Odds</i> <i>Ratio</i> = 3.509, 95% Confidence Interval: 1.056-11.656, <i>P</i> = 0.040). <i>Malassezia globosa</i> was associated with the tumor size (<i>P</i> = 0.031) and PD-L1 status (<i>P</i> = 0.024). GC patients with a high abundance of <i>Malassezia globosa</i> had shorter OS than others (<i>P</i> = 0.028). <i>Malassezia globosa</i> was an independent factor (<i>Hazard</i> <i>Ratio</i> = 3.080, 95% Confidence Interval: 1.140-8.323, <i>P</i> = 0.027) for OS after adjusting for tumor stage. <i>Malassezia globosa</i> was figured out to be associated with- fatty acid and lipid biosynthesis and degradation via LIPASYN pathway. <i>Conclusions. Malassezia globosa</i> 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.