Identification and Validation of Apparent Imbalanced Epi-lncRNAs Prognostic Model Based on Multi-Omics Data in Pancreatic Cancer

Abstract

<b>Background:</b> Globally, pancreatic adenocarcinoma is a recognized cause of pancreatic death (PAAD) associated with high mortality. Long non-coding RNAs (lncRNAs) play an important role in several biological processes in pancreatic cancer. <b>Methods:</b> The gene expression profile of PAAD patients were obtained from The Cancer Genome Atlas (TCGA) database. The <i>limma</i> package was used to identify epigenetic disorders of lncRNAs and PCG. Subsequently, the genomic characteristics and landscape of lncRNAs were explored. The pancreatic cancer-related lncRNAs gene set from Lnc2Cancer v3.0 were collected and the difference between cancer samples and normal samples were analysed. A prognostic model consisting of five epigenetic lncRNA (epi-lncRNAs) was established by univariate and multivariate Cox proportional hazards regression analyses and was verified across different data sets. Finally, the expression of core epi-lncRNAs was identified by PCR experiment. <b>Results:</b> A total of 2237 epi-lncRNAs, 11855 non-epi-lncRNAs, 13518 epi-PCGs, and 6097 non-epi-PCGs, were identified. The abnormal frequency of lncRNAs in pancreatic cancer was much lower than that in PCG, and 138 epi-lncRNAs were enriched in human cancer-related lncRNAs. Epi-lncRNAs had a higher number with longer lengths and a greater number of transcripts. Epi-lncRNAs associated with epigenetic disorders had a higher number of exons, gene length, and isomers as compared to non-epi-lncRNAs. Further, the five pancreatic cancer-specific epi-lncRNA genes (AL161431.1, LINC00663, LINC00941, SNHG10, and TM4SF1-AS1) were identified. Based on these five pancreatic cancer-specific epis-lncRNAs, a prognostic model for pancreatic cancer was established. The RT-PCR result confirmed that AL161431.1, LINC00663, LINC00941, and SNHG10 expressions in pancreatic cancer samples were higher as compared to normal pancreatic samples; the expression of TM4SF1-AS1 in pancreatic cancer cells was significantly lower than that in normal pancreatic samples. <b>Conclusions:</b> Epigenetic abnormalities could promote abnormal lncRNA expression in pancreatic cancer and may play an important role in its progression.