Abstract
BackgroundExtensive research has revealed that genes play a pivotal role in tumor development and growth. However, the underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further.MethodsIn this study, we identified overlapping differentially expressed genes (DEGs) by comparing tumor tissue with adjacent normal tissue using the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database.ResultsOur analysis identified 79 up-regulated and ten down-regulated genes. Functional enrichment analysis and prognosis analysis were conducted on the identified genes, and the fatty aldehyde dehydrogenase (FALDH) gene, ALDH3A2, was chosen for more detailed analysis. We performed Gene Set Enrichment Analysis (GSEA) and immunocorrelation analysis (infiltration, copy number alterations, and checkpoints) to elucidate the mechanisms of action of ALDH3A2 in depth. The immunohistochemical (IHC) result based on 140 paraffin-embedded human GC samples indicated that ALDH3A2 was over-expressed in low-grade GC cases and the OS of patients with low expression of ALDH3A2 was significantly shorter than those with high ALDH3A2 expression. In vitro results indicated that the expression of ALDH3A2 was negatively correlated with PDCD1, PDCD1LG2, and CTLA-4.ConclusionWe conclude that ALDH3A2 might be useful as a potential reference value for the relief and immunotherapy of GC, and also as an independent predictive marker for the prognosis of GC.
Highlights
Extensive research has revealed that genes play a pivotal role in tumor development and growth
These 89 differential genes were mapped as a heatmap using the data from the Cancer Genome Atlas (TCGA)-Stomach adenocarcinomas (STAD) (Fig. 2f)
We examined the relationship between immune cell expression and survival, and discovered that elevated numbers of macrophages might predict a worse prognosis in STAD (P = 0.004; Fig. 6e)
Summary
Extensive research has revealed that genes play a pivotal role in tumor development and growth. The underlying involvement of gene expression in gastric carcinoma (GC) remains to be investigated further. GC arises from the epithelial cells of the gastric mucosa and is a common malignancy of the digestive system that results in an estimated 990,000 new cases and 738,000 deaths each year [1]. The combined application of multiple treatments, including surgery, chemotherapy, radiotherapy, and targeted gene therapy, has markedly improved the survival rate of GC. Studies from Wong et al and Sawaoka H et al indicated that COX2, a membrane conjugated protein, might play a pivotal role in cell proliferation, apoptosis, angiogenesis, and gastric carcinogenesis [5, 6].
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