M6A Regulator Expression Could Pattern Predict The Immune Microenvironment And Prognosis Of Non-Small Cell Lung Cancer

BackgroundM6A methylation modification is one of the most common m RNA modifications,which is involved in a variety of biological processes,such as cell death,cancer stem cell formation and tumorigenesis.More and more evidences show that the expression pattern of m6 A regulatory factor is significantly related to the PD-L1 level of some solid tumors,but few studies have explored the role of m6 A regulatory factor in the immune microenvironment and prognosis of non-small cell lung cancer(NSCLC)and its different subtypes.MethodsWith the help of R language,the expression profile data of non-small cell lung cancer in TCGA public data were analyzed.Firstly,the genes differentially expressed by m6 A regulator in NSCLC were identified.Then,the independent survival analysis of20 m6 A regulators was conducted to explore their prognostic value in NSCLC,and the prognostic risk model was constructed based on the expression profile of m6 A regulators in NSCLC,and was divided into high and low risk groups.In addition,the influence of m6 A on the immune microenvironment of NSCLC was revealed by analyzing the correlation between 22 kinds of immune infiltrating cells and m6 A regulatory factors.Finally,in order to explore the function of m6 A as a biomarker of anti-PD-L1 therapeutic effect,we explored the relationship between tumor mutation burden(TMB)and PD-L1 expression level and the expression patterns of 20 m6 A regulatory genes in NSCLC.At the same time,the common subtypes of lung squamous cell carcinoma and lung adenocarcinoma of NSCLC were also analyzed in the same way to further analyze the effect of m6 A on non-small cell lung cancer.ResultsFirst of all,20 m6 A regulatory factors were differentially expressed in NSCLC,and the regulatory factors were closely linked and played a role through mutual coordination.The IGF2 BP protein family had the most significant differential expression in different subtypes,which might play a potential role in differentiating different NSCLC subtypes,guiding treatment and predicting prognosis.In the construction of the prognosis model,METTL3,HNRNPC and VIRMA genes were significantly associated with the prognosis of NSCLC patients.In particular,Cox regression analysis confirmed that METTL3 could be used as an independent prognostic factor to predict the survival of NSCLC patients,and HNRNPA2B1,IGF2BP1 and HNRNPC were independent risk factors to affect the prognosis of lung adenocarcinoma.In addition,m6 A had different ability to predict the prognosis of different subtypes of NSCLC and changed the degree of immune infiltration.M6 A shown better advantages in lung adenocarcinoma,and METTL3 and HNRNPA2B1 might affect the prognosis of NSCLC by regulating the immune microenvironment.Finally,the high expression of IGF2BP3 and HNPNPC could improve the prognosis of lung adenocarcinoma,which showed a good correlation with tumor mutation burden in lung adenocarcinoma.There was no similar finding in lung squamous cell carcinoma.The IGF2 BP protein family,YTHDC2 and other regulatory factors were significantly correlated with the expression level of PD-L1,indicating the existence of m6 A methylation regulatory factors that could predict the therapeutic effect of anti-PD-L1 treatment.ConclusionOur study found that some m6 A regulatory factors were independent risk factors for the prognosis of NSCLC,and identified m6 A regulatory factors related to immune infiltration,tumor mutation burden and PD-L1 level in NSCLC,and the correlation was different in different subtypes,which was more obvious in lung adenocarcinoma.In conclusion,M6 A regulatory factor could be used as a biomarker to predict the prognosis and immunotherapy of NSCLC patients.