Construction of an efferocytosis-related long non-coding ribonucleic acid scoring system to predict clinical outcome and immunotherapy response in pancreatic adenocarcinoma

Background: Efferocytosis suppresses antitumour immune responses by inducing the release and secretion of cytokines. Long non-coding ribonucleic acids (lncRNAs) have various functions in different forms of programmed cell death and in immune regulation. This study aims to explore the potential role of efferocytosis-related lncRNAs as biomarkers in pancreatic adenocarcinoma (PAAD).

Methods: Transcriptome profiles, simple nucleotide variations and clinical data of patients with PAAD were extracted from The Cancer Genome Atlas (TCGA) database. Co-expression algorithms identified efferocytosis-related lncRNAs. The efferocytosis-related lncRNA scoring system (ERLncSys) was established using Cox regression and the Least Absolute Shrinkage and Selection Operator algorithm. Additionally, Kaplan-Meier (K-M) curves, Cox regression, receiver operating characteristic (ROC) curves and clinical parameter stratification analyses were used to evaluate ERlncSys. Moreover, ERlncSys was explored through Gene Set Variation Analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Furthermore, the TIMER platform, ESTIMATE algorithm, single sample Gene Set Enrichment Analysis and immune checkpoint analysis were utilised to explore the predictive power of ERlncSys for the tumour immune microenvironment (TIME). Finally, a consensus clustering algorithm identified distinct molecular profiles among patients with PAAD, aiding in the identification of potential beneficiaries for immunotherapy.

Results: K-M, Cox regression and ROC analyses confirmed the robust prognostic efficacy of ERlncSys. Clinical stratification analysis indicated the broad applicability of ERlncSys in PAAD. Additionally, mmunological analyses indicated that ERlncSys can determine immune cell infiltration status in the TIME. Furthermore, consensus clustering analysis based on ERlncSys divided the TCGA-PAAD cohort into two clusters. Cluster 1 exhibited characteristics consistent with an immune 'hot tumour' compared to cluster 2, suggesting cluster 1 is a more suitable population for immune checkpoint inhibitor therapy.

Conclusion: The established ErlncSys aids in predicting the prognosis and understanding the TIME landscape of patients with PAAD. In turn, it facilitates the identification of optimal candidates for immunotherapy. This study introduces novel insights into the potential value of efferocytosis-related lncRNAs as biomarkers in PAAD.