Identification of Grb2-associated binding protein 3 expression to predict clinical outcomes and immunotherapeutic responses in lung adenocarcinoma.

Abstract

With the deepening research on tumor microenvironment (TME), immunotherapy has been deemed to be one of the major breakthroughs for cancer therapy. Nevertheless, only some patients respond well to this treatment. It is vital to explore predictive biomarkers for clinical benefit of immunotherapy. Grb2-associated binding protein 3 (GAB3) exerts essential biological functions in ovarian cancer and colorectal cancer. The potential role of GAB3 in lung adenocarcinoma (LUAD) has not been fully elucidated. RNA-sequencing data, genetic mutation data, and matched clinical data were obtained from the cancer genome atlas (TCGA) databases, then underwent gene expression, prognosis, enrichment, TME, immune checkpoint blockade (ICB) response analyses utilizing R packages. The mRNA expression level of GAB3 was dramatically decreased in LUAD, and the prognostic analysis indicated that the patients with low GAB3 expression performed unsatisfactory clinical outcomes. In addition, differentially expressed genes (DEGs) and subsequent functional enrichment analysis demonstrated that GAB3 was primarily connected with T cell activation and immune response. Finally, GAB3 expression positively correlated with immune infiltrates and immune checkpoint genes, and therapeutic effect of ICB. In summary, our study comprehensively uncovers that GAB3 may function as a promising biomarker to predict clinical outcomes and immunotherapeutic responses in LUAD patients.