Construction of immune related prognostic model for pancreatic ductal adenocarcinoma based on single cell RNA-seq analysis

Abstract

There are no reliable biomarkers for early diagnosis and prognosis evaluation in pancreatic ductal adenocarcinoma (PDAC). Single cell RNA-seq (scRNA-seq) revealed tumor microenvironment heterogeneity in PDAC. This study aimed to construct immune-related prognostic model of PDAC based on scRNA-seq. Multiple scRNA-seq datasets for PDAC were retrieved from online databases and combined with scRNA-seq results from and our previous study. The malignant ductal cells were identified through calculating CNV scores. The common immune related signatures were identified to develop prognostic model using scRNA-seq and TCGA_PAAD datasets. The expression and distribution of key signature gene SPP1 was explored by scRNA-seq and multicolor immunohistochemistry. The robust markers of malignant ductal cells in PDAC were found. Five immune-related signatures, including SPP1, LINC00683, SNHG10, LINC00237, CASC19 were used to develop risk score formula to predict the overall survival of PDAC patients. We also constructed an easy-to-use nomogram, combining risk score, N stage, and margin status of PDAC. The expression level of SPP1 was related to the prognosis and immune regulators. In addition, we found that SPP1 was mainly expressed in ductal cells and macrophages in PDAC. In conclusion, we constructed a promising prognostic model based on immune related genes and LncRNAs for PDAC using scRNA-seq and TCGA_PAAD datasets.

Rescue Blood Contamination in scRNA-Seq Data by Originator, a Computational Deciphering Tool using Genetic and Contextual Information

“…Two datasets are used in this report. One is a PDAC scRNA-Seq dataset, in which two tumor tissues are used in this study (GSE212966) [7]. The other is the scRNA-Seq data from placenta tissues,comprising eight placenta samples from the previous study (EGA; https://www.ebi.ac.uk/ega/) hosted by the European Bioinformatics Institute (EBI; accession no.…”

“…We first applied Originator to a pancreatic ductal adenocarcinoma (PDAC) scRNA-seq dataset [7], to demonstrate its utility in removing cells that originate from blood. Originator successfully separates immune cells in the blood from those in the tumor tissue ( For example, CCL4 and CCL5 expression is higher in T-cells in the tumor tissue compared to those in the blood (Supplementary Figure 2a), consistent with the previous study that these genes are directly associated with T-cell-inflamed phenotype and antigen-presenting cell mediated processes in PDAC [8].…”