Identification of Ubiquitin-Related Gene-Pair Signatures for Predicting Tumor Microenvironment Infiltration and Drug Sensitivity of Lung Adenocarcinoma

SIMPLE SUMMARY: Lung adenocarcinoma (LUAD) has a high mortality and incidence rate. The therapeutic efficacy of LUAD varies with the individual heterogeneity of the tumor microenvironment (TME). It is necessary to explore more biomarkers and targets to improve the prognosis of patients. Ubiquitination pathways are involved in the biological process of regulating the anti-tumor immunity of immune cells and immunosuppression of tumor cells in the TME of patients. In this study, we clarified the characteristics of ubiquitin-related gene pairs (UbRGPs) and identified the relationship between the status of the TME and UbRGPs of patients with LUAD. A prognostic signature based on six UbRGPs was established, which performed well in predicting the immune infiltration and tumor mutation burden (TMB) in the TME and the response of LUAD to immuno-, chemo-, and targeted therapy. In conclusion, the UbRGPs signature is an independent prognostic indicator and has great potential in assisting the clinical therapy for patients with LUAD. ABSTRACT: Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer worldwide, and new biomarkers are urgently required to guide more effective individualized therapy for patients. Ubiquitin-related genes (UbRGs) partially participate in the initiation and progression of lung cancer. In this study, we used ubiquitin-related gene pairs (UbRGPs) in tumor tissues to access the function of UbRGs in overall survival, immunocyte infiltration, and tumor mutation burden (TMB) of patients with LUAD from The Cancer Genome Atlas (TCGA) database. In addition, we constructed a prognostic signature based on six UbRGPs and evaluated its performance in an internal (TCGA testing set) and an external validation set (GSE13213). The prognostic signature revealed that risk scores were negatively correlated with the overall survival, immunocyte infiltration, and expression of immune checkpoint inhibitor-related genes and positively correlated with the TMB. Patients in the high-risk group showed higher sensitivity to partially targeted and chemotherapeutic drugs than those in the low-risk group. This study contributes to the understanding of the characteristics of UbRGPs in LUAD and provides guidance for effective immuno-, chemo-, and targeted therapy.