Comprehensive analysis of disulfidptosis-related lncRNAs for predicting prognosis and response of immunotherapy in pancreatic adenocarcinoma

Transl Cancer Res. 2024 Mar 31;13(3):1336-1350. doi: 10.21037/tcr-23-1706. Epub 2024 Mar 27.

Abstract

Background: Pancreatic adenocarcinoma (PAAD) is a common and deadly tumor. Currently, there is a severe lack of therapeutic options. As a novel mode of cell death, increasing evidence reveals the important role of the disulfidptosis in cancer. However, few studies have utilized disulfidptosis-related long-stranded non-coding RNAs (DRlncRNAs) to investigate the prognosis of PAAD.

Methods: We comprehensively analyzed the expression and prognostic value of 958 DRlncRNAs in PAAD using data from The Cancer Genome Atlas (TCGA). We established and validated a new DRlncRNAs-related prognostic index by least absolute shrinkage and selection operator (LASSO) and COX regression analysis. In addition, we built a nomogram consisting of risk score, age, gender, tumor grade and stage to validate the clinical feasibility of the index. We further evaluated the value of the index in terms of PAAD functional pathways, tumor microenvironment (TME) and tumor mutations.

Results: We designed a risk model for five DRlncRNAs and demonstrated its accuracy using receiver operating characteristic (ROC) curves. COX regression suggested that the model may be an independent predictor of cancer prognosis. Tumor immune infiltration analysis revealed that low-risk subgroups had higher extent of immune infiltration, higher sensitivity to immunotherapy and a higher TME score. This is helpful for us to discover more precise immunotherapy for PAAD patients.

Conclusions: In conclusion, we established a DRlncRNA index comprising of five DRlncRNAs, which may provide new insights for clinical diagnosis and precision therapy.

Keywords: Pancreatic adenocarcinoma (PAAD); disulfidptosis; immunotherapy response; long-stranded non-coding RNA (lncRNA); prognosis.