Clinical Value Of M6A,m5C And M1A-related LncRNA In The Prognosis Of Pancreatic Cancer And Response To Immunotherapy

Objective: To investigate the prognostic value of long-stranded non-coding RNA(lnc RNA)associated with m6 A,m5C and m1 A and pancreatic adenocarcinoma(PC)and their immunotherapeutic response.Methods: Patients with pancreatic cancer were screened from The Cancer Genome Atlas(TCGA)database,and univariate,LASSO and multivariate Cox regression were used to obtain m6 A,m5c and m1A-associated lnc RNAs by using Pearson correlation as criteria to construct a prognostic model for PC.Validation was performed by Kaplan-Meier survival analysis and subject operating characteristic curve(ROC).The column line graph model was constructed by combining risk score and clinical characteristics,and its performance was evaluated by ROC and other methods,and the correlation of,m6 A,m5C and m1A-related lnc RNA markers with somatic mutation number,immune cell infiltration,immune function,immune checkpoint(ICIs),tumor microenvironment(TME)score and chemotherapeutic drug sensitivity was analyzed.Results: Eight lnc RNA were screened for significant correlation with overall survival(OS)of PC patients,and multifactorial Cox analysis was performed to obtain three Lnc RNA(AC005332.6,AC096733.2,AC090114.2)for constructing the prognostic risk model.Using the median risk score as the threshold,the model was divided into high-risk and low-risk groups,suggesting that the OS of the high-risk group was lower than that of the low-risk group;the risk score was an independent prognostic factor for PC patients,and the column line graph incorporating the risk score had better predictive performance.Most immune checkpoint genes were significantly different between the two risk groups(P <0.05);immune microenvironment analysis showed that the abundance of immune infiltrating cells,etc.,was lower in the high-risk group than in the low-risk group(P <0.05);overall survival was lower in patients with high tumor mutation burden(TMB)than in patients with low TMB;drug sensitivity was lower in patients in the low-risk group to Navitoclax,Ponatinib and Axitinib were more sensitive in the low-risk group,while patients in the high-risk group were sensitive to A-443654 and A-770041.Conclusions:The bioinformatics analysis method was able to screen and select three lnc RNAs associated with PC prognosis: AC005332.6,AC096733.2,AC090114.2;the risk model based on these three genes can better predict the prognosis of PC patients;the application of this model may help to make clinical decisions on immunotherapy for pancreatic cancer.