Identification of ubiquitinated substrate proteins and their gene expression patterns in lung adenocarcinoma

Abstract

Background: Lung cancer is a malignant disease with the highest cancer-related mortality rate. In lung adenocarcinoma (LUAD), protein ubiquitination can regulate multiple biological processes. A LUAD ubiquitylome analysis has not yet been reported. Methods:We used for the first time ion mobility into liquid chromatography-mass spectrometry to perform accurate and reliable ubiquitylome and proteomic analysis of clinical LUAD and normal tissues and combined it with transcriptome data obtained from public databases. Ubiquitinated protein substrates and their gene expression pattern landscapes in LUAD were identified using bioinformatics methods.Results: Our data revealed a ubiquitination landscape in LUAD and identified characteristic protein ubiquitination motifs. We found that the ubiquitinated peptide motifs in LUAD were completely different from those of previously published lung squamous cell carcinoma (LUSC). Moreover, we identified two gene expression patterns of ubiquitinated proteins and revealed that survival differences between these patterns may be correlated with the tumor immune infiltrating microenvironment. Finally, we constructed a prognostic predictive model to quantify the relationship between expression patterns and survival. We found a relationship between the patient-applied model score and multiple drug sensitivity. Therefore, our model can serve as a guide for LUAD clinical treatment.Conclusions: Our work addresses the lack of ubiquitylome studies in LUAD and provides new perspectives for subsequent research and clinical treatment.

Biological effects of COVID-19 on lung cancer: Can we drive our decisions

“…Besides studying these important protein receptors, which are considered to drive the entry of the virus into cells, researchers have also started to analyze the molecular profiles of the genes associated with the mutational patterns of the relevant targets ( 79 , 80 ). These considerations were derived from the recent discovery of a possible correlation between the membrane proteins and lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) ( 81 , 82 ). Specifically, these mutations have not only been detected but are also related to patient survival.…”