The Role Of UBE2T In The Prognosis Of NSCLC And Mechanisms Exploration

Background:As one of the most important factors threatening the life and health of human,lung cancer ranks first among all cancers’ incidence and morality.China has the largest burden of lung cancer in the world,and more than 1/3 of the new cases are in China.Non-small cell lung cancer accounts for about 85% of lung cancer,although great achievement has been made in the treatment of non-small cell lung cancer in recent years,the 5-year survival rate remains low,so there is still a long way to go to identify novel diagnostic molecular markers and therapeutic targets and further clarify mechanisms of non-small cell lung cancer.Ubiquitination is one of most common post-translational modifications of proteins,which plays an important role in the physiological regulation of body and development of diseases through affecting protein functions.Ubiquitin conjugating enzyme E2 is an important member of the ubiquitinase family,which binds the ubiquitin activated by the ubiquitin activating enzyme E1,then the ubiquitin is transferred to the protein substrates through ubiquitin ligase E3 to regulate the functions of proteins.Ubiquitin conjugating enzyme E2 T(UBE2T)is one of the E2 s,which was first reported in Fanconi anemia,and in recent years,more and more studies have shown that UBE2 T also plays an important role in cancers,but the role of UBE2 T in the development of non-small cell lung cancer and its prognostic value are not so clear.Objective:To study the relationship between UBE2 T and clinical features of non-small cell lung cancer and its prognostic value,and explore its possible mechanism in the occurrence and development of non-small cell lung cancer.Methods:Download RNA-seq and clinical data of non-small cell lung cancer patients from CHOICE study,Wilcoxon test and univariate logistic regression are used to analyze the relationship between UBE2 T m RNA and clinical features.Kaplan-Meier Plotter Lung Cancer database is used to study the prognostic value of UBE2 T m RNA.UBE2 T immunohistochemistry is performed on tissue sections of 206 patients with stage IB-IIIA lung adenocarcinoma in the Second Affiliated Hospital of Zhejiang University(SAHZU)to analyze the relationship between UBE2 T protein expression and clinical characteristics.Correlation analysis,GO enrichment analysis and GSEA are applied to explore the possible mechanism of UBE2 T in the occurrence and development of non-small cell lung cancer.Results:(1)UBE2T m RNA is higher in non-small cell lung cancer tissues compared with matched adjacent tissues,and high UBE2 T m RNA is positively correlated with male,smoking,squamous cell carcinoma,high stage,and lymph node metastasis.(2)Patients with higher UBE2 T m RNA have a shorter overall survival,especially among smokers,adenocarcinoma,Stage I,T1 patients and patients without lymph nodes and distant metastases.(3)Patients with higher UBE2 T m RNA have a shorter progression free survival,particularly among non-smokers,adenocarcinoma and Stage I patients.(4)UBE2T protein expression is correlated with the degree of differentiation of lung adenocarcinoma,and the higher the expression,the lower the differentiation.(5)GO enrichment analysis and GSEA indicate that UBE2 T may participate in the processes such as cell cycle,DNA damage checkpoint,p53 signaling pathway,oxidative phosphorylation,glycolysis,unfolded protein response and so on.(6)GSEA suggest that UBE2 T may interact with E2 F transcription factor,MYC,PI3 K,AKT,m TOR,m TORC1 complex and so on.Conclusion:(1)UBE2T is correlated with the degree of differentiation of non-small cell lung cancer,and the higher the expression,the higher the degree of malignancy.(2)Non-small cell lung cancer patients with high UBE2 T m RNA have a worse prognosis.(3)UBE2T may participate in the processes such as cell cycle,DNA damage checkpoint,p53 signaling pathway,oxidative phosphorylation,glycolysis,unfolded protein response and so on to regulate the occurrence and development of non-small cell lung cancer.(4)UBE2T may interact with E2 F transcription factor,MYC,PI3 K,AKT,m TOR,m TORC1 complex and so on to regulate the occurrence and development of non-small cell lung cancer.