A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer

Cancer Cell Int. 2020 Oct 9:20:493. doi: 10.1186/s12935-020-01588-y. eCollection 2020.

Abstract

Background: Pancreatic cancer (PC) is one of the most common cancers and the leading cause of cancer-related death worldwide. Exploring novel predictive biomarkers for PC patients' prognosis is in urgent need.

Methods: In the present study, we conducted Cox proportional hazards regression to identify critical prognosis-associated lncRNAs (PALncs) in TCGA PC dataset. Based on the results of multivariate analysis, a PALnc-based risk score system was established, and validated in GSE62452 dataset. The validity and reliability of the risk score system for prognosis of PC were evaluated through ROC analysis. And function enrichment analyses for the PALncs were also performed.

Result: In the multivariate analysis, four PALncs (LINC00476, C9orf163, LINC00346 and DSCR9) were screened out to develop a risk score system, which showed a high AUC at 3 and 5 years overall survival (0.785 at 3 year OS, 0.863 at 5 year OS) in TCGA datasets. And the ROC analysis of the risk score system for RFS in TCGA dataset revealed that AUC for RFS was 0.799 at 3 years and 0.909 at 5 years. Further, the AUC for OS in the validation cohort was 0.705 at 3 years and 0.959 at 5 years. Furthermore, the functional enrichment analysis revealed that these PALncs may be involved in various pathways related to cancer, including Ras family activation, autophagy in cancer, MAPK signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, etc. And correlation analysis of these tumor infiltrating immune cells and risk score system revealed that the infiltration level of B cell naïve, plasma cells, and CD8+ T cells are negatively correlated to the risk score system, while macrophages M2 positively correlated to the risk score system.

Conclusion: Our study established a four PALncs based risk score system, which reflects immune cell infiltration and predicts patient survival for PC.

Keywords: Biomarker; Pancreatic cancer; Risk score; TCGA; lncRNAs.