Comprehensive analysis identifies ARHGEF6 as a potential prognostic and immunological biomarker in lung adenocarcinoma

Lung adenocarcinoma (LUAD), the most common histological type in lung cancer, is one of leading cancers with considerable morbidity/mortality worldwide. Treating LUAD remains an outstanding challenge due to the lack of early diagnosis and the poor therapeutic effects. Rac/Cdc42 guanine nucleotide exchange factor 6 (ARHGEF6), one of cytoskeletal regulators, exerts crucial biological functions in T cell migration. The potential biological role of ARHGEF6 in LUAD has yet to be established. Using multiple bioinformatics tools and statistical methods, we discovered that the mRNA and protein expression level of ARHGEF6 was significantly downregulated in tumor tissues comparing to normal controls. Moreover, ARHGEF6 presented high diagnostic value in LUAD patients (AUC = 0.949), and the patients with low ARHGEF6 expression had more somatic mutations and poor T stage, N stage, clinical prognosis. Experimental validation indicated that ARHGEF6 was low expressed in A549 and PC-9 cells comparing to the normal lung epithelial cells. The overexpression of ARHGEF6 remarkably attenuated the abilities of cell proliferation and colony formation. Furthermore, the immune landscape analysis in TME revealed that ARHGEF6 expression was positively associated with immune cell infiltration and immune checkpoints. Single-cell transcriptome analysis indicated that ARHGEF6 expression was also distributed in immune cell types in TME based on TISCH database. Additionally, differentially expressed genes (DEGs) and functional enrichment analyses uncovered that ARHGEF6 was involved in T cell activation. Finally, LUAD samples were classified two clusters based on DEGs for subgroups analysis. In summary, this study comprehensively uncovered that ARH-GEF6 could be identified as a potential prognostic and immunological biomarker in lung adenocarcinoma.

Automated summary

This study found that ARHGEF6 was significantly downregulated in lung adenocarcinoma tissues and had high diagnostic value. Low expression of ARHGEF6 was associated with more somatic mutations, worse tumor stage, and poor clinical prognosis. Experimental validation showed that low expression of ARHGEF6 inhibited cell proliferation and colony formation. Additionally, ARHGEF6 expression was positively correlated with immune cell infiltration and immune checkpoints. Overall, ARHGEF6 could be a potential prognostic and immunological biomarker in lung adenocarcinoma.