Integrated single-cell and bulk RNA sequencing revealed the molecular characteristics and prognostic roles of neutrophils in pancreatic cancer.

ABSTRACT

Pancreatic cancer, one of the most prevalent tumors of the digestive system, has a dismal prognosis. Cancer of the pancreas is distinguished by an inflammatory tumor microenvironment rich in fibroblasts and different immune cells. Neutrophils are important immune cells that infiltrate the microenvironment of pancreatic cancer tumors. The purpose of this work was to examine the complex mechanism by which neutrophils influence the carcinogenesis and development of pancreatic cancer and to construct a survival prediction model based on neutrophil marker genes. We incorporated the GSE111672 dataset, comprising RNA expression data from 27,000 cells obtained from 3 patients with PC, and conducted single-cell data analysis. Thorough investigation of pancreatic cancer single-cell RNA sequencing data found 350 neutrophil marker genes. Using The Cancer Genome Atlas (TCGA), GSE28735, GSE62452, GSE57495, and GSE85916 datasets to gather pancreatic cancer tissue transcriptome data, and consistent clustering was used to identify two categories for analyzing the influence of neutrophils on pancreatic cancer. Using the Random Forest algorithm and Cox regression analysis, a survival prediction model for pancreatic cancer was developed, the model showed independent performance for survival prognosis, clinic pathological features, immune infiltration, and drug sensitivity. Multivariate Cox analysis findings revealed that the risk scores derived from predictive models is independent prognostic markers for pancreatic patients. In conclusion, based on neutrophil marker genes, this research created a molecular typing and prognostic grading system for pancreatic cancer, this system was very accurate in predicting the prognosis, tumor immune microenvironment status, and pharmacological treatment responsiveness of pancreatic cancer patients.