A four prognosis-associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patie

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Cancer Cell International Open Access

A four prognosis‑associated lncRNAs (PALnc) based risk score system reflects immune cell infiltration and predicts patient survival in pancreatic cancer Hongkai Zhuang1,2, Shanzhou Huang1, Zixuan Zhou1,3, Zuyi Ma1,2, Zedan Zhang1,2, Chuanzhao Zhang1* and Baohua Hou1* 

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 prognosisassociated 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:  Pancreatic cancer, Biomarker, lncRNAs, Risk score, TCGA​

*Correspondence: [email protected]; [email protected] 1 Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106 Zhongshan Er Road, Guangzhou 510080, China Full list of author information is available at the end of the article

Background As one of the most aggressive cancers, pancreatic cancer (PC) caused 4.5% of all cancer related deaths in 2015 globally [1]. The prognosis of PC patients could be varied due to the characteristic of heterogeneity. There are some clinical risk factors, e.g. tumor size, vessel invasion, etc., which are associated with patients survival [2]. However,

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use,