Aerial View of the Association between m6A-Related LncRNAs and Clinicopathological Characteristics of Pancreatic Cancer
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Abstract
Abstract Background There have been few reports on how long non-coding RNA (lncRNA) under the regulation of N6-methyladenosine (m6A) modification influences pancreatic cancer progression. In our study, the association between m6A-related lncRNAs and pancreatic ductal adenocarcinoma (PDAC) was comprehensively described for the first time based on the construction of a lncRNAs prognostic model. Methods The lncRNAs expression level and the prognostic value were investigated in 440 PDAC patients and 171 normal tissues from Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and International Cancer Genome Consortium (ICGC) databases. We implemented Pearson correlation analysis to explore the m6A-related lncRNAs, univariate Cox regression and Kaplan-Meier (K-M) methods were performed to screen the critical lncRNAs in PDAC patients. Then we used bioinformatic analysis and statistical analysis to illustrate the association between m6A-related lncRNAs and pancreatic cancer. Results Seven prognostic m6A-related lncRNAs were identified as prognostic lncRNAs, and they were inputted in the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to establish an m6A-related lncRNAs prognostic model in the TCGA database. Each patient has calculated a risk score and divided into low-risk and high-risk subgroups by the median value in two cohorts. Moreover, the model showed a robust prognostic ability in the stratification analysis of different risk subgroups, pathological grades, and recurrence events. The Cox regression demonstrated that the risk classification was an independent prognostic predictor. We established a competing endogenous RNA (ceRNA) network based on seven pivotal lncRNAs and twenty-six m6A regulators. Enrichment analysis indicated that malignancy-associated biological function and signaling pathways were enriched in the high-risk subgroup and m6A-related lncRNAs target mRNAs. We have even identified small molecule drugs that may affect the progression of pancreatic cancer. Conclusions In conclusion, we provide the first comprehensive aerial view between m6A-related lncRNAs and pancreatic cancer's clinicopathological characteristics.
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