Chordin-Like 2: A Possible Therapeutic Target for Gastric Cancer by Affecting Cell Cycle and Proliferation

Abstract

This study aimed to examine the role of chordin-like 2 (CHRDL2) in gastric cancer. The Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets were screened and the differentially expressed gene CHRDL2 was identified. The CHRDL2 expression was examined in the Human Protein Atlas and TCGA. Clinical data on gastric cancer were evaluated for their association with CHRDL2 by using TCGA and KM-plotter databases. The possible relationship amongst CHRDL2, immune cells, and related genes was investigated via the TIMER database. Enrichment analysis was performed using GO and KEGG pathways to explore the mechanisms. Screening of databases revealed that CHRDL2 was a differentially expressed gene. An increase in cytoplasmic CHRDL2 expression was found in cancer tissues compared with the surrounding normal tissues. The data, together with those from TCGA and the KM-plotter databases, showed that patients with gastric cancer with high level of CHRDL2 have worse prognosis than those with low expression. A strong correlation was found between CHRDL2 expression and T stage, race, pathological grade, and pathological type according to clinical data analysis. CHRDL2 expression is linked to immune infiltration, as shown by the TIMER database. The data suggested that CHRDL2 plays a pivotal role in the tumor microenvironment of gastric cancer and might help tumor cells evade the immune system. Gene set enrichment analysis showed that CHRDL2 is involved in the chemokine signaling route, the intestinal immune network, the MAPK pathway, cell cycle, and the PI3K-Akt signaling system that are associated with the pathological processes of gastric cancer. Patients with gastric cancer with decreased CHRDL2 levels have dramatically improved OS, PFS, and PPS. CHRDL2 plays a pivotal role in enabling tumor cell immune evasion in tumor microenvironment, suggesting a function of this gene in the development of gastric cancer and its immune infiltration. Interfering with CHRDL2 may slow down the development of this malignancy by affecting cell cycle and apoptosis pathways.