Identification of Malassezia globosa as a Gastric Fungus Associated with PD-L1 Expression and Overall Survival of Patients with Gastric Cancer
Zhenzhan Zhang, Yaopeng Qiu, Hao Feng, Donghua Huang, Bin-shu Weng, Zhou Xu, Qingfeng Xie, Zhe Wang, Wenfu Ding, Guoxin Li, Hao Liu
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 ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>C</a:mi> <a:mi>P</a:mi> <a:mi>S</a:mi> <a:mo>≥</a:mo> <a:mn>10</a:mn> </a:math> ) and PD-L1-Low group ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>C</c:mi> <c:mi>P</c:mi> <c:mi>S</c:mi> <c:mo><</c:mo> <c:mn>10</c:mn> </c:math> ) by principal coordinates analysis (PCoA) ( <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>=</e:mo> <e:mn>0.014</e:mn> </e:math> for Bray-Curtis and <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo>=</g:mo> <g:mn>0.042</g:mn> </g:math> for Jaccard). Malassezia had a higher abundance in the PD-L1-High group compared to the PD-L1-Low group ( <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>=</i:mo> <i:mn>0.045</i:mn> </i:math> ). 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 ( <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mi>P</k:mi> <k:mo>=</k:mo> <k:mn>0.047</k:mn> </k:math> ). Malassezia globosa was associated with PD-L1 expression ( <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mi>O</m:mi> <m:mi>d</m:mi> <m:mi>d</m:mi> <m:mi>s</m:mi> <m:mtext> </m:mtext> <m:mi>R</m:mi> <m:mi>a</m:mi> <m:mi>t</m:mi> <m:mi>i</m:mi> <m:mi>o</m:mi> <m:mo>=</m:mo> <m:mn>3.509</m:mn> </m:math> , 95% Confidence Interval: 1.056-11.656, <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mi>P</o:mi> <o:mo>=</o:mo> <o:mn>0.040</o:mn> </o:math> ). Malassezia globosa was associated with the tumor size ( <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>P</q:mi> <q:mo>=</q:mo> <q:mn>0.031</q:mn> </q:math> ) and PD-L1 status ( <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>P</s:mi> <s:mo>=</s:mo> <s:mn>0.024</s:mn> </s:math> ). GC patients with a high abundance of Malassezia globosa had shorter OS than others ( <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mi>P</u:mi> <u:mo>=</u:mo> <u:mn>0.028</u:mn> </u:math> ). Malassezia globosa was an independent factor ( <w:math xmlns:w="http://www.w3.org/1998/Math/MathML" id="M12"> <w:mi>H</w:mi> <w:mi>a</w:mi> <w:mi>z</w:mi> <w:mi>a</w:mi> <w:mi>r</w:mi> <w:mi>d</w:mi> <w:mtext> </w:mtext> <w:mi>R</w:mi> <w:mi>a</w:mi> <w:mi>t</w:mi> <w:mi>i</w:mi> <w:mi>o</w:mi> <w:mo>=</w:mo> <w:mn>3.080</w:mn> </w:math> , 95% Confidence Interval: 1.140-8.323, <y:math xmlns:y="http://www.w3.org/1998/Math/MathML" id="M13"> <y:mi>P</y:mi> <y:mo>=</y:mo> <y:mn>0.027</y:mn> </y:math> ) 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.