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

Ran Xu; Tong Lu; Jiaying Zhao; Qi Li; Jun Wang; Bo Peng; Jian Liu; Pengfei Zhang; Lidong Qu; Xiaoyan Chang; Lingqi Yao; Linyou Zhang

doi:10.21037/atm-21-5645

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

Ann Transl Med. 2021 Nov;9(22):1692. doi: 10.21037/atm-21-5645.

Authors

Ran Xu^{1

2}, Tong Lu^{1

2}, Jiaying Zhao^{1

2}, Qi Li³, Jun Wang^{1

2}, Bo Peng^{1

2}, Jian Liu^{1

2}, Pengfei Zhang^{1

2}, Lidong Qu^{1

2}, Xiaoyan Chang^{1

2}, Lingqi Yao^{1

2}, Linyou Zhang¹

Affiliations

¹ Department of Thoracic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
² The Second Clinical Medical College, Harbin Medical University, Harbin, China.
³ Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, China.

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.

Keywords: Lung adenocarcinoma (LUAD); prognosis; proteasome; proteomic; ubiquitylome.