Identification of a novel signature for prognostic stratification and integrative analyses in lung adenocarcinoma.

BACKGROUND: Recently, research has revealed that the Golgi apparatus is involved in the development process of cancer; however, the specific effect of Golgi apparatus-related genes (GAGs) in lung adenocarcinoma (LUAD) remains unclear. This study aims to construct a more concise and practical risk model in LUAD using GAG. METHODS: The gene expression profiles of patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and GAGs were downloaded from the Gene Set Enrichment Analysis (GSEA) database. Univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were performed to identify the prognostic GAG signature. Kaplan-Meier and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signatures. The correlation between the risk model and the immune landscape was examined using CIBERSORT and TIDE analyses. Also, the genes in the signature were assessed by single-cell RNA sequencing (scRNA-seq). RESULTS: A prognostic signature comprising 5 GAG genes (GNPNAT1, RGS20, CAV3, NTSR1, and FURIN) was established after LASSO and multi-Cox analyses. Both the Kaplan-Meier analysis and the ROC curves supported the strong predictive utility of the risk model. Specifically, the former yielded significant stratification in all three validation datasets (P=1.2001e-05, P=0.006, and P=0.04), while the latter provided further evidence of its predictive precision through the area under the curve. In addition, we found that the low-risk group responded better to immunotherapy than the high-risk group (P<0.0001). scRNA-seq analysis revealed the distribution patterns of the 5 GAG genes in cells. Finally, we assessed the situation of tumor mutation burden (TMB) and performed functional analysis based on the risk model of GAGs. CONCLUSIONS: The risk model based on GAGs can effectively stratify the prognosis of patients and predict immunotherapy responses in LUAD.