Identification of Robust Immune‐Associated lncRNAs Signature for Immune Checkpoint Blockade and Prognosis in Pancreatic Ductal Adenocarcinoma

Abstract

Background: An increasing body of evidence has suggested that long non-coding RNAs (lncRNAs) can serve as essential regulators in cancer immunity. We aimed to establish a robust immune-associated lncRNA signature for pancreatic ductal adenocarcinoma (PDAC) outcome prediction to enhance prognostic accuracy.Methods: Pancreatic cancer samples were obtained from the The Cancer Genome Atlas (TCGA) project. Immune‐related lncRNAs displaying significant association with overall survival (OS) were screened through univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. The prediction reliability was further estimated in the internal validation set and combination set. Gene set enrichment analysis (GSEA) of the lncRNA model risk score was performed for functional annotation. The correlation between immune checkpoint inhibitors and this signature was examined. Results: 5 immune-related lncRNAs were confirmed to establish five‐immune-related lncRNAs prognostic signature. The constructed risk model showed significant correlation with PDAC OS. The area under the curve (AUC) for this lncRNA model was up to 0.747. This immune‐related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our signature mediated chondrocyte development, laminin binding and so forth. This risk score model was associated with immune cell infiltration (i.e., CD4 T cells, etc.,) and immune checkpoint blockade (ICB) immunotherapy‐related molecules (i.e., PDCD1 and CTLA4).Conclusion: The immune‐related lncRNA signature we established possesses latent prognostic value for patients with PDAC and may have the potential to measure the response to ICB immunotherapy, which could guide for immunological treatment in PDAC.

An Independent Prognostic Model Based on Ten Autophagy-Related Long Noncoding RNAs in Pancreatic Cancer Patients

“…(4) LINC02257 was expressed at high levels in colorectal cancer patients and seemed to act as a hazard factor [ 38 ]. Xu et al noted that LINC02257 and FLVCR1-DT were utilized as an adverse lncRNA and favorable lncRNA, respectively, for monitoring the model-based prognosis prediction of PC patients [ 39 ]. RPTOR is one of the ATGs interacting with LINC02257; a study found that the expression of miR-377-3p could target RPTOR and induce autophagy in vivo and in vitro [ 40 ].…”