Abstract
Precision medicine for gastric cancer (GC) is still an unsolved issue, because most available target drugs are not specifically designed for GC. Exploring novel signaling molecules with target value for GC is in urgent need. This study aimed to reveal that interleukin-2 receptor subunit gamma (IL2RG) is such a key molecule in human GC progression. GC tissues and paracancerous gastric tissues were collected from 7 patients (5 males and 2 females) during tumor radical excision surgery. These tissues were used to identify the differentially expressed genes (DEGs) with RNA-seq and serial bioinformatics analyses including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene expression profiling interactive analysis (GEPIA), and survival analysis. RT-qPCR and western blotting were performed to compare the mRNA and protein expression levels of IL2RG between GC tissues and adjacent normal gastric tissues as well as between GC cell line SGC-7901 and normal gastric epithelial cell line GES-1. Results showed striking elevations of IL2RG both in the mRNA and protein levels in GC tissues and human gastric cancer SGC-7901 cell line compared, respectively, with the adjacent normal gastric tissues and normal GES-1 cells, and higher IL2RG expression was associated with lower survival. Analyses on the GSE29272 and GSE15459 datasets from Gene Expression Omnibus verified that IL2RG was highly expressed in GC patients and was associated with poor overall survival. In addition, molecular docking showed that a small molecule, resatorvid (TAK 242), might be an inhibitor of IL2RG. We conclude that IL2RG is overexpressed in advanced GC and is associated with low survival. IL2RG may serve as a biomarker of GC progression and poor prognosis.
Highlights
Gastric cancer (GC) has a mortality rate of the third place and a 5-year survival rate of less than 30% [1]. e high incidence of gastric cancer (GC) in the world is mainly reported in East Asia
We reported the differentially expressed genes (DEGs) in the male GC and the female GC tissues relatively to the adjacent normal gastric tissues and analyzed the functions of these DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and identified the potential key gene involved in the enriched pathways
Comparing with the normal gastric tissues from females, the DEGs associated with cytokine receptor interaction (CCRI) were enriched in female GC tissues
Summary
Gastric cancer (GC) has a mortality rate of the third place and a 5-year survival rate of less than 30% [1]. e high incidence of GC in the world is mainly reported in East Asia. Gastric cancer (GC) has a mortality rate of the third place and a 5-year survival rate of less than 30% [1]. Current clinical diagnosis and treatment have been developing, GC patients are often diagnosed in the late stage, while metastasis and recurrence may occur after radical excision in the early stage. E pathogenesis of GC is not fully clear [2, 3], and this situation leads to difficulties in early diagnosis, treatment, and prognosis. Human epidermal growth factor receptor-2 (HER2), the first identified protein associated with breast cancer, is found overexpressed in GC [4]. Trastuzumab, a humanized monoclonal antibody designed for HER2, has been used in the therapy metastatic GC, but its safety evaluation is still lacking. Unlike treatment of breast cancer, trastuzumab used in GC does not appear to be effective after
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