Predicting pancreatic cancer outcome with necrosis-associated long noncoding RNAs

Abstract

Abstract Background: The pathogenesis of pancreatic cancer remains elusive, despite its high mortality rate and limited therapeutic efficacy. Therefore, it is imperative to explore the potential role of necrosis in the pathogenesis of pancreatic cancer. Methods: Gene expression and clinical data were from The Cancer Genome Atlas (TCGA) database . To identify long non-coding RNA (lncRNA), we conducted co-expression analysis using immune genes from the database. The risk model was constructed by employing univariate and multivariate Cox regressions, as well as Lasso penalized regression analysis. Then, the patients were divided into high-risk and low-risk groups. Subsequently, we conducted an assessment of our signature across diverse clinical settings, encompassing clinical-pathological characteristics, tumor-infiltrating immune cells, and checkpoint-related biomarkers.Prognostic prediction was achieved by integrating differentially expressed long non-coding RNA (lncRNA) signatures associated with necroptosis. We constructed a highly predictive nomogram by fusing necrosis related lncRNA signature with clinical features. Results: We generated lncRNA signatures by considering the variations in the expression of different lncRNAs.The AUC of the ROC curve, which pertains to the signature's predictive ability for the 5-year survival rate, was determined to be 0.918. Further analysis demonstrated that our signature is capable of effectively differentiating unfavorable survival outcomes, prognostic clinic-pathological characteristics, and accurately determining tumor infiltration status. We found a significant correlation between the low risk group and the high expression of immune checkpoint related genes. Conclusion: A pancreatic cancer lncRNA signature of innovative nature, demonstrating promising prognostic value, was developed through the utilization of the TCGA database. Our research can provide valuable evidence for the diagnosis, treatment, and prognosis evaluation of pancreatic cancer.