Investigation and verification of GAMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma

Abstract

Background and aim: It has been reported GIMAP6 was crucial for autophagy. But it is unknown the role of GIMAP6 in occurrence and tumor-immunity of lung adenocarcinoma. Methods: Comprehensive analyses for datasets from TCGA and GTEx databases were conducted by R software. Basic experiments including RT-qPCR, CCK-8 assays, colony formation assay and transwell assays were applied to explore the role of GIMAP6 in vivo and vitro. Prognostic features and GIMAP6 were applied to construct nomogram. Potential mechanism of GIMAP6 in lung adenocarcinoma was investigated by GO, KEGG and GESA. The correlation between GIMAP6 and immune landscape has also been explored using scRNA sequencing datasets from Timer 2.0 and TISCH. Results: The OS and DSS of lung adenocarcinoma patients with high GIMAP6 expression was better than that with low GIMAP6 expression. The nomogram based on T stage, N stage, and GIMAP6 had predictive significance for prognosis, which was identified by ROC and calibration curve. Functional enrichment analysis suggested that GIMAP6 was mainly involved in T-cell receptor signaling pathway, chemokine signaling pathway, cytokine and cytokine receptor interaction. Single cell sequencing and TIMER2.0 analysis illustrated that GIMAP6 was positively correlated with the infiltration of immune cells and immune-relate molecules including CTLA4, PD-L1, and TIGIT. Basic experiments confirmed the role of GIMAP6 in the proliferation, invasion and migration of lung adenocarcinoma cells. Conclusion: We confirmed that GIMAP6 was an effective prognostic molecule and involved in the regulation of the immune microenvironment of lung adenocarcinoma, which may become a predictor for the efficacy of immunotherapy.