关键词: 肺腺癌, 鞘脂代谢, 细胞凋亡, 癌基因, DEGS2

Abstract:

Objective: To investigate the expression trends of all genes in normal lung tissues, paracancerous tissues and lung adenocarcinoma tissues, screen for characteristic genes and verify their functions via experiments. Methods: Integrated datasets of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were retrieved from the University of California, Santa Cruz (UCSC) Data Portal. R software was applied to analyze the expression trends of all genes, identify characteristic genes, and extract the gene set co-expressed at high levels in both paracancerous and tumor tissues. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Genes with the most significant expression alterations in the most enriched pathway were screened among normal lung tissues, paracancerous tissues and lung adenocarcinoma tissues. The role of candidate genes in tumorigenesis was validated using cell biology experiments. Results: Integrated data analysis identified a cluster of genes (DEGS2, PIGY, FUCA, GM2A) that were lowly expressed in normal tissues but highly expressed in both paracancerous and lung adenocarcinoma tissues. GO enrichment analysis demonstrated that these genes were most significantly enriched in the membrane lipid metabolic process pathway. Intersection analysis of genes involved in this pathway and those consistent with the aforementioned expression trend revealed that DEGS2 exhibited the most prominent upregulation in paracancerous and tumor tissues, with an upregulation fold change of 3.27 compared with normal tissues. Cell experiments confirmed that DEGS2 knockout led to a significant reduction in the migration ability of lung adenocarcinoma cells at 24 h post-transfection, and a 55.0% decrease in cell viability at 72 h post-transfection. Conclusion: DEGS2 is highly expressed in both paracancerous tissues and lung adenocarcinoma tissues. This elevated expression can promote the proliferation and migration of lung adenocarcinoma cells, thereby driving the progression from paracancerous tissues to malignant tumors.

Key words: Lung adenocarcinoma, Sphingolipids metabolism, Apoptosis, Oncogenes, DEGS2