Relationship Between CNVs and Immune Cells Infiltration in Gastric Tumor Microenvironment

Abstract

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.

Delving into the Heterogeneity of Different Breast Cancer Subtypes and the Prognostic Models Utilizing scRNA-Seq and Bulk RNA-Seq

“…Control cells which contain 500 B cells, 500 T cells and 500 endothelial cells were randomly selected, serving as cells with a normal copy number, and the random seed was set to 123 to ensure reproducibility [ 33 ]. Normal epithelial cells and cancer cells were separated by checking the iterative clustering effect and calculating the copy number variation score [ 34 , 35 ].…”

Clinical implications of lncRNA LINC-PINT in cancer

“…However, exploiting the potential of lncRNAs as biomarkers and therapeutic targets is just the beginning (Mirzaei et al, 2022). For example, lncRNAs associated with immune checkpoints (Li et al, 2022a;Jiang et al, 2022;Wen et al, 2022) have been used as disease biomarkers in the new wave of cancer immunotherapy that is currently revolutionizing oncology practice (Figure 1A). Nevertheless, small successes in the clinical setting are expected to help build confidence in lncRNAs as biomarkers and produce the momentum needed for their broader applications.…”

Carboxypeptidase vitellogenic like facilitates resistance to CDK4/6 inhibitors in breast cancer

“…9,10 Little is known about CPVL due to a paucity of studies. [11][12][13] However, CPVL promotes glioma progression through Bruton tyrosine kinase/adenovirus early region 1Abinding protein p300-mediated reduction in signal transducer and activator of transcription 1 phosphorylation. CPVL is a promising marker of gastric cancer and its gene mutations are associated with type 2 diabetic retinopathy.…”

“…The probable serine carboxypeptidase vitellogenic like (CPVL) comprises 477 amino acids and belongs to the carboxypeptidase family 9,10 . Little is known about CPVL due to a paucity of studies 11–13 . However, CPVL promotes glioma progression through Bruton tyrosine kinase/adenovirus early region 1A‐binding protein p300‐mediated reduction in signal transducer and activator of transcription 1 phosphorylation.…”