AUTHOR=Li Fazhan , Wen Huijuan , Bukhari Ihtisham , Liu Bin , Guo Chenxu , Ren FeiFei , Tang Youcai , Mi Yang , Zheng Pengyuan 

TITLE=Relationship Between CNVs and Immune Cells Infiltration in Gastric Tumor Microenvironment

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.869967

DOI=10.3389/fgene.2022.869967

ISSN=1664-8021

ABSTRACT=<p>Gastric cancer (GC) is a highly fatal and common malignancy of the digestive system. Recent therapeutic advancements have significantly improved the clinical outcomes in GC, but due to the unavailability of suitable molecular targets, a large number of patients do not respond to the immune checkpoint inhibitors (ICI) therapy. To identify and validate potential therapeutic and prognostic targets of gastric cancer, we used the “inferCNV” R package for analyzing single-cell sequencing data (GSE112302) of GC and normal epithelial cells. First, by using LASSO, we screened genes that were highly correlated with copy number variations (CNVs). Therefrom, five gene signature (<italic>CPVL</italic>, <italic>DDC</italic>, <italic>GRTP1</italic>, <italic>ONECUT2</italic>, and <italic>PRSS21</italic>) was selected by cross-validating the prognosis and risk management with the GC RNA-seq data obtained from GEO and TCGA. Moreover, the correlation analyses between CNVs of these genes and immune cell infiltration in gastric cancer identified <italic>CPVL</italic> as a potential prognostic marker. Finally, <italic>CPVL</italic> showed high expression in gastric cancer samples and cell lines, then siRNA-mediated silencing of <italic>CPVL</italic> expression in gastric cancer cells showed significant proliferation arrest in MGC803 cells. Here, we conclude that CNVs are key regulators of the immune cells infiltration in gastric TME as well as cancer development, and <italic>CPVL</italic> could potentially be used as a prognostic and therapeutic marker in gastric cancer.</p>