The potential use and experimental validation of genomic instability-related lncRNA in pancreatic carcinoma

Abstract

This study explored the potential role of long noncoding RNA (lncRNAs) associated with genomic instability in the diagnosis and treatment of pancreatic adenocarcinoma (PAAD). Transcriptome and single-nucleotide variation data of PAAD samples were downloaded from the cancer genome atlas database to explore genomic instability-associated lncRNAs. We constructed a genomic instability-associated lncRNA prognostic signature. Then gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were used to explore the physiological role of lncRNAs involved in genomic instability. Tumor microenvironments, immunotherapy response, immune cell infiltration, immune checkpoint, and drug sensitivity were compared between high-risk and low-risk groups. In vitro experiments were performed for external validation. Six lncRNAs associated with genomic instability were identified, capable of predicting the prognosis of PAAD. Patients were assigned to low-risk or high-risk groups using these biomarkers, with better or worse prognosis, respectively. The tumor immune score, immune cell infiltration, and efficacy of immunotherapy were worse in the high-risk group. A drug sensitivity analysis revealed the high- and low-risk groups had different half-maximal inhibitory concentrations. The expression of cancer susceptibility candidate 8 was significantly higher in tumor tissues than in normal tissues, while the expression of LYPLAL1-AS1 exhibited an opposite pattern. They may be potential diagnostic or prognostic biomarkers for patients with pancreatic cancer. Genomic instability-associated lncRNAs were explored in this study and predicted the prognosis of PAAD and stratified patients risk in PAAD. These lncRNAs also predicted the efficacy of immunotherapy and potential therapeutic targets in PAAD.