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

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.

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

“…For example, proteasomal inhibitors that block the ubiquitin-proteasome pathway have been approved and used effectively in clinical trials for the treatment of multiple myeloma [34]. Previous studies have also established ubiquitin-related signatures for other cancer types such as lung adenocarcinoma, hepatocellular carcinoma, and glioma [35][36][37][38]. Hence, we developed a novel gene expression signature based on a screen on a collection of UbRGs and determined its prognostic significance in OV (Figures 2 and 3).…”

A novel model based on ubiquitination-related gene to predict prognosis and immunotherapy response in hepatocellular carcinoma

“…URGs have been considered as controllers of tumors, impacting the regulation of tumor cell cycle, expression of genes, and advancement [ 12 ]. Nowadays, many scholars have applied URGs related characteristics to forecast the future course and immune reaction of various types of cancer, such as lung adenocarcinoma and endometrial cancer, the prognostic signature based on URGs performed well in predicting the infiltration of immune cells and the level of tumor mutation burden (TMB) within the TME and the effectiveness of immunotherapy for cancer treatment [ 13 , 14 ]. There were several studies have uncovered the relationship of URGs and the initiation and development of HCC, nevertheless, the role of URGs in HCC has not been systematically analyzed [ 15 , 16 ].…”

Prognostic implication and immunotherapy response prediction of a novel ubiquitination-related gene signature in liver cancer

“…The previous studies extensively explored the incorporation of transcriptomics and ubiquitination, using statistical testing and machine learning. This led to significant advancements and established ubiquitination as a crucial characteristic of cancer [ 13 , 16 , 17 ]. Aberrations in the ubiquitination process may contribute to the diverse nature of lung cancer.…”