The mitotic spindle-related seven-gene predicts the prognosis and immune microenvironment of lung adenocarcinoma

Abstract

Abstract Purpose Abnormalities in the mitotic spindle have been linked to a variety of cancers. Data on their role in the onset, progression, and treatment of lung adenocarcinoma (LUAD) need to be explored. Methods The data were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Molecular Signatures Database (MSigDB), for the training cohort, external validation cohort, and the hallmark mitotic spindle gene set, respectively. Mitotic spindle genes linked to LUAD prognosis were identified and intersected with differentially expressed up-regulated genes in the training cohort. Nomogram prediction models were built based on least absolute shrinkage and selection operator (LASSO) regression, univariate cox, and multivariate cox analyses. The seven-gene immunological score was examined, as well as the correlation of immune checkpoints. The DLGAP5 and KIF15 expression in BEAS-2B, A549, H1299, H1975, and PC-9 cell lines was validated with western blot (WB). Results A total of 965 differentially expressed up-regulated genes in the training cohort intersected with 51 mitotic spindle genes associated with LUAD prognosis. Finally, the seven-gene risk score was determined and integrated with clinical characteristics to construct the nomogram model. Immune cell correlation analysis revealed a negative correlation between seven-gene expression with B cell, endothelial cell (excluding LMNB1), and T cell CD8 + (p < 0.05). However, the seven-gene expression was positively correlated with multiple immune checkpoints (p < 0.05). The expression of DLGAP5 and KIF15 were significantly higher in A549, H1299, H1975, and PC-9 cell lines than that in BEAS-2B cell line. Conclusion High expression of the seven genes is positively correlated with poor prognosis of LUAD, and these genes are promising as prospective immunotherapy targets.