SPAG5 Expression Predicts Poor Prognosis and is Associated With Adverse Immune Infiltration in Lung Adenocarcinomas.

Background: Sperm-associated antigen 5 (SPAG5) has been identified as a novel driver oncogene involved in multiple cancers; however, its role in lung adenocarcinoma (LUAD) needs further investigation. Our study aims to elucidate the potential significance of SPAG5 in LUAD prognosis and its implications for the efficacy of immunotherapy. Methods: In this study, we used bioinformatics analysis and tissue microarray (TMA) staining to examine the potential role of SPAG5 in LUAD survival and response to immunotherapy. We used the Oncomine, TIMER2.0, Gene Expression Profiling Interactive Analysis (GEPIA), Sangerbox, PredicScan, and Kaplan-Meier Plotter databases to examine the expression and prognostic role of SPAG5 in the LUAD of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other databases. We also used Cancer Single-cell State Atlas (CancerSEA) and Tumor Immune Estimation Resource (TIMER2.0) to analyze the association of SPAG5 with malignant phenotype and tumor immune microenvironment. Furthermore, Immune Cell Abundance Identifier (ImmuCellAI) analysis of TCGA sequencing data was used to predict the role of SPAG5 in determining the response to immune checkpoint blockade (ICB) treatment in LUAD. Co-expression analysis of programmed death-ligand 1 (PD-L1) and SPAG5 was performed using LUAD TMA immunohistochemistry (IHC) analysis. Results: Our findings indicate that SPAG5 is overexpressed in LUAD and is positively correlated with advanced clinical stage, poor overall survival, relapse-free survival, and progression-free survival outcomes. SPAG5 may be involved in regulating the cell cycle, proliferation, invasion, DNA damage and repair, and tumor immunosuppression. Furthermore, TMA IHC analysis showed a positive correlation between PD-L1 expression in LUAD and SPAG5 which suggests that SPAG5 may serve as a potential predictor of response to ICB therapy in LUAD. Conclusions: Our results highlight the role of SAPG5 in promoting a tumor malignancy phenotype and immunosuppression in LUAD and suggest that SPAG5 may serve as a potential response marker for ICB therapy.