Relationship Between CNVs and Immune Cells Infiltration in Gastric Tumor Microenvironment

Frontiers in Genetics

卷:13

Fazhan Li¹  Chenxu Guo¹  Bin Liu¹  Huijuan Wen¹  FeiFei Ren¹  Pengyuan Zheng²  Yang Mi²  Youcai Tang³  Ihtisham Bukhari⁴ 

[1] Academy of Medical Science, Zhengzhou University, Zhengzhou, China;

[2] Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

[3] Department of Pediatrics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

[4] Henan Key Laboratory of Helicobacter Pylori, Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

关键词: gastric cancer;    cancer immunotherapy;    immune infiltration;    copy number variation;    tumor microenvironment;   

DOI  :  10.3389/fgene.2022.869967

来源: DOAJ

【 摘 要 】

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 (CPVL, DDC, GRTP1, ONECUT2, and PRSS21) 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 CPVL as a potential prognostic marker. Finally, CPVL showed high expression in gastric cancer samples and cell lines, then siRNA-mediated silencing of CPVL 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 CPVL could potentially be used as a prognostic and therapeutic marker in gastric cancer.

【 授权许可】

Unknown