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Identification of prognostic immune-related lncRNAs in pancreatic cancer

FRONTIERS IN IMMUNOLOGY(2022)

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Abstract
Long noncoding RNAs (lncRNAs) play a critical role in the immune regulation and tumor microenvironment of pancreatic cancer (PaCa). To construct a novel immune-related prognostic risk model for PaCa and evaluate the prognostic prediction of lncRNAs, essential immune-related lncRNAs (IRlncRNAs) were identified by Pearson correlation analysis of differentially expressed immune-related genes (IRGs) and IRlncRNAs in PaCa from The Cancer Genome Atlas (TCGA) and GTEx databases. Least absolute shrinkage and selection operator (LASSO) regression was also applied to construct a prognostic risk model of IRlncRNAs, and gene set enrichment analysis (GSEA) was further applied for functional annotation for these IRlncRNAs. A total of 148 IRlncRNAs were identified in PaCa to construct a prognostic risk model. Among them, lncRNA LINC02325, FNDC1-AS1, and ZEB2-AS1 were significantly upregulated in 69 pairs of PaCa tissues by qRT-PCR. ROC analyses showed that LINC02325 (AUC = 0.80), FNDC1-AS1 (AUC = 0.76), and ZEB2-AS1 (AUC = 0.75) had a good predictive effect on 5-year survival prognosis. We demonstrated that high expression levels of ZEB2-AS1 and LINC02325 were not only positively associated with tumor size and CA199, but elevated levels of ZEB2-AS1 and FNDC1-AS1 were also positively correlated with tumor stage. GSEA further revealed that immune-related pathways were mainly enriched in the high-risk groups. Several immune-related algorithms demonstrated that four IRlncRNAs were related to immune infiltration, immune checkpoints, and immune-related functions. Thus, the prognostic risk model based on IRlncRNAs in Paca indicates that the four IRlncRNA signatures may serve as predictors of survival and potential predictive biomarkers of the pancreatic tumor immune response.
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Key words
pancreatic cancer,immune infiltration,prognostic model,lncRNAs,irlncRNAs
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