Transcriptomic investigation highlights tumor suppressive effects of TAGAP in lung adenocarcinoma

Abstract Background: The role of the T cell-activated Rho GTPase activating protein (TAGAP) in immune diseases continues to be explored but has not been yet elucidated for lung adenocarcinoma (LUAD).Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression dataset (GTEx) databases were used to analyze the difference of TAGAP expression and its correlation with immune cell infiltration, immune checkpoints, and tumor cell stemness scores in pan-cancer and LUAD cohorts. Gene expression single-cell sequencing data from Gene Expression Omnibus (GEO) were used to analyze TAGAP distribution in immune cells. The correlation between TAGAP expression and immune cell markers was validated in 26 pairs of LUAD tissues by Reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemistry. Results: TAGAP was differentially expressed in 27 different cancers tissues and the corresponding adjacent tissues. Its expression level was significantly correlated with immune cell infiltration, immune checkpoints, mDNAsi, and mRNAsi. Moreover, TAGAP was significantly low in LUAD and could be associated with poor prognosis, thereby it can be used as an independent prognostic factor for LUAD. Besides, TAGAP showed a significant positive correlation with B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in LUAD. The experimental verification with RT-qPCR and immunohistochemistry showed that TAGAP was significantly positively correlated with CD8 and CD4 expressions. TAGAP expression is linked to a greater response to immune checkpoint blockade treatment in NSCLC. Conclusion: Overall, TAGAP can be a potential LUAD biomarker and might play anti-tumor effects by enhancing the tumor immune cell infiltration in LUAD’s microenvironment, TAGAP might be used as an immunotherapy target to regulate the anti-tumor immune response.