Abstract
BackgroundIncreasing evidence shows that the ubiquitin–proteasome system has a crucial impact on lung adenocarcinoma. However, reliable prognostic signatures based on ubiquitination and immune traits have not yet been established.MethodsBioinformatics was performed to analyze the characteristic of ubiquitination in lung adenocarcinoma. Principal component analysis was employed to identify the difference between lung adenocarcinoma and adjacent tissue. The ubiquitin prognostic risk model was constructed by multivariate Cox regression and least absolute shrinkage and selection operator regression based on the public database The Cancer Genome Atlas, with evaluation of the time-dependent receiver operating characteristic curve. A variety of algorithms was used to analyze the immune traits of model stratification. Meanwhile, the drug response sensitivity for subgroups was predicted by the “pRRophetic” package based on the database of the Cancer Genome Project.ResultsThe expression of ubiquitin genes was different in the tumor and in the adjacent tissue. The ubiquitin model was superior to the clinical indexes, and four validation datasets verified the prognostic effect. Additionally, the stratification of the model reflected distinct immune landscapes and mutation traits. The low-risk group was infiltrating plenty of immune cells and highly expressed major histocompatibility complex and immune genes, which illustrated that these patients could benefit from immune treatment. The high-risk group showed higher mutation and tumor mutation burden. Integrating the tumor mutation burden and the immune score revealed the patient’s discrepancy between survival and drug response. Finally, we discovered that the drug targeting ubiquitin and proteasome would be a beneficial prospective treatment for lung adenocarcinoma.ConclusionThe ubiquitin trait could reflect the prognosis of lung adenocarcinoma, and it might shed light on the development of novel ubiquitin biomarkers and targeted therapy for lung adenocarcinoma.
Highlights
It has been extensively acknowledged that lung cancer is strikingly the most common cancer among the whole population (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths)
To research the signature of ubiquitin molecules in patients of Lung adenocarcinoma (LUAD), 2,838 ubiquitination genes were screened, including those encoding E1s, E2s, E3s, and DUBs, which originated from the IUUCD
A total of 181 genes of ubiquitination were co-expressed in the TCGA and Gene Expression Omnibus (GEO) databases (Figure 2A)
Summary
It has been extensively acknowledged that lung cancer is strikingly the most common cancer among the whole population (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths). It has the potency to modify tumor-associated proteins and further degrade them in a proteasome-dependent manner that makes the malfunction of ubiquitination an adverse capacity to cause LUAD inclusively [4,5,6,7,8,9]. Ubiquitination correlates with the regulation of T cell receptor proximal signaling, which acts as a critical component of adaptive immunity. These results indicated that ubiquitination is involved in extensive antitumor immunity but failed to describe its explicit role in regulating immune cells and their environment. The exploration of ubiquitination in regulating immune response and its correlation with genome alternation in lung adenocarcinoma needs further evaluation. Reliable prognostic signatures based on ubiquitination and immune traits have not yet been established
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