Prognostic Value of Drug Targets Predicted Using Deep Bioinformatic Analysis of m6A-Associated lncRNA-Based Pancreatic Cancer Model Characteristics and Its Tumour Microenvironment.

Abstract

The role of N6-methyladenosine (m6A)-associated long-stranded non-coding RNA (lncRNA) in pancreatic cancer is unclear. Therefore, we analysed the characteristics and tumour microenvironment in pancreatic cancer and determined the value of m6A-related lncRNAs for prognosis and drug target prediction. An m6A-lncRNA co-expression network was constructed using The Cancer Genome Atlas database to screen m6A-related lncRNAs. Prognosis-related lncRNAs were screened using univariate Cox regression; patients were divided into high- and low-risk groups and randomised into training and test groups. In the training group, least absolute shrinkage and selection operator (LASSO) was used for regression analysis and to construct a prognostic model, which was validated in the test group. Tumor mutational burden (TMB), immune evasion, and immune function of risk genes were analysed using R; drug sensitivity and potential drugs were examined using the Genomics of Drug Sensitivity in Cancer database. We screened 129 m6A-related lncRNAs; 17 prognosis-related m6A-related lncRNAs were obtained using multivariate analysis and three m6A-related lncRNAs (AC092171.5, MEG9, and AC002091.1) were screened using LASSO regression. Survival rates were significantly higher (p < 0.05) in the low-risk than in the high-risk group. Risk score was an independent predictor affecting survival (p < 0.001), with the highest risk score being obtained by calculating the c-index. The TMB significantly differed between the high- and low-risk groups (p < 0.05). In the high- and low-risk groups, mutations were detected in 61 of 70 samples and 49 of 71 samples, respectively, with KRAS, TP53, and SMAD4 showing the highest mutation frequencies in both groups. A lower survival rate was observed in patients with a high versus low TMB. Immune function HLA, Cytolytic activity, and Inflammation-promoting, T cell co-inhibition, Check-point, and T cell co-stimulation significantly differed in different subgroups (p < 0.05). Immune evasion scores were significantly higher in the high-risk group than in the low-risk group. Eight sensitive drugs were screened: ABT.888, ATRA, AP.24534, AG.014699, ABT.263, axitinib, A.443654, and A.770041. We screened m6A-related lncRNAs using bioinformatics, constructed a prognosis-related model, explored TMB and immune function differences in pancreatic cancer, and identified potential therapeutic agents, providing a foundation for further studies of pancreatic cancer diagnosis and treatment.