DLGAP5 作为肺腺癌生物标志物的生物信息学分析：对免疫浸润和靶向治疗的意义

Lung cancer is a leading cause of cancer-related deaths globally, and its lack of early symptoms and lack of effective screening tools result in many patients being diagnosed at a late stage, which significantly reduces the five-year survival rate. Consequently, this research sought to identify novel molecular biomarkers for the early detection of lung adenocarcinoma (LUAD) and to evaluate the prognostic outcomes for affected patients. METHOD: We extracted differentially expressed genes from three datasets (GSE140797, GSE43458, GSE31210) associated with lung adenocarcinoma (LUAD) from the GEO database and screened them for intersections, resulting in the identification of 402 genes. Subsequently, 15 hub genes of significance were identified using Cytoscape analysis. Further, COX regression analysis was performed on these 15 genes in the TCGA database, and the key gene DLGAP5, associated with prognosis, was finally screened out. Based on the TIMER, GEPIA, and TCGA database results, we found that DLGAP5 showed a high expression level in LUAD patients. Utilizing data from the TCGA database regarding DLGAP5 expression levels, we categorized tumor patients into two groups: those with high and those with low expression. We then conducted survival analyses and assessments of TNM staging to investigate the connection between DLGAP5, patient prognosis, and clinical tumor classification. Meanwhile, the specific biological functions of DLGAP5 in LUAD patients were assessed by GO and KEGG enrichment analysis. In addition, ESTIMATE, CIBERSORT, and ssGSEA methods were used to assess the tumor immune infiltration in LUAD patients. Finally, we analyzed the relationship between DLGAP5 expression and immune checkpoints, tumor mutational load (TMB), and drug sensitivity, and provided a final assessment of its prognostic value. RESULT: In lung adenocarcinoma (LUAD), there was a notable increase in the expression of DLGAP5, which correlated with a worse prognosis. The expression exhibited a strong positive relationship with TH2 cells and natural killer (NK) cells while showing a negative relationship with B cells, dendritic cells, and mast cells. In addition, high expression of DLGAP5 was associated with the cell cycle, p53 signaling pathway, and folate biosynthesis pathway, whereas its low expression was associated with neuroactive ligand-receptor interactions, pancreatic secretion, exogenous drug metabolism by cytochrome P450, bile secretion, and arachidonic acid metabolism pathway. Meanwhile, this study also found that a variety of important immune checkpoints were significantly and positively correlated with the expression of DLGAP5, a higher tumor mutation load index, and the IC50 values of those with low DLGAP5 expression showed an increasing trend.

DLGAP5 exhibits generally high expression levels in lung adenocarcinoma (LUAD), which is associated with mutations in key driver genes, poorer prognosis, and enrichment with immune infiltration pathways. Moreover, the elevated levels of DLGAP5 were linked to the increased expression of genes related to immune checkpoint blockade. This suggests that DLGAP5 may influence patient outcomes by modulating the tumor microenvironment and shaping potential immunotherapy targets. Therefore, DLGAP5 is expected to be a novel molecular biomarker for predicting the prognosis of LUAD and evaluating the efficacy of immunotherapy.