Construction Of A Necroptosis-related Prognostic Model In Evaluating The Prognosis Of Patients With Pancreatic Cancer

Background: Pancreatic cancer(PC)is a common solid malignancy with a high incidence and very poor prognosis.It is often not diagnosed early and the best time for treatment is missed when it is detected.Currently,the early treatment is surgery,and when surgery is not possible,a combination of radiotherapy and immunotherapy can be used to improve the patient’s prognosis.Globally,the incidence of pancreatic cancer is on the rise,posing a serious threat to people’s health.Pancreatic cancer is a common tumor of the gastrointestinal tract with a very poor prognosis.At present,clinical imaging and biochemical indicators cannot effectively assess the prognosis of patients,so it is meaningful to find a marker that can more accurately assess the prognosis of patients.A large body of literature indicates that necrotizing apoptosis plays a crucial role in the development and progression of cancer.In pancreatic cancer,the significance of necrotizing apoptosis still needs to be explored.Objective: To investigate the role and prognostic value of necroptosis in pancreatic cancer,as well as to construct prognostic models based on genes associated with necroptosis and to identify risk subgroups of pancreatic cancer patients and to guide clinical decision making.Also the difference of immune microenvironment between different groups was explored.Methods: The pancreatic cancer transcriptome data were obtained from the TCGA database,ICGC database and GSE85916 from the GEO database;the TCGA cohort was set as a training cohort,and the ICGC and GSE85916 cohorts were set as validation cohorts.The single-cell sequencing data of pancreatic cancer were obtained from GSE154778 in the GEO database,and the genes most associated with necrosis were identified by weighted co-expression network analysis and single-cell sequencing analysis.COX regression and Lasso regression were performed on these genes and prognostic models were developed.Patients with pancreatic cancer were divided into NCPTS＿high and NCPTS＿low groups by calculating risk scores,and survival analysis,immunofiltering analysis,and mutation analysis between groups were performed.The expression of EPS8 was further verified by q RT-PCR assay on clinical samples.Results: We constructed a necrosis-related signature of pancreatic cancer using single-cell sequencing analysis and transcriptome analysis.The calculated results The risk score formula was as follows:NCPTS = POLR3 GL *(-0.404)+ COL17A1 *0.092+ DDIT4 * 0.007+ PDE4 C * 0.057+ CLDN1 * 0.075 + HMGA2 * 0.056 + CENPF * 0.198 +EPS8 * 0.219.By this feature,it was possible to divide the different cohorts of pancreatic cancer patients into NCPTS＿high and NCPTS＿low groups NCPTS＿high group had a significantly worse prognosis.Significant differences were found between the two groups in the level of immune endofiltration and the level of mutations.EPS8 expression was detected by clinical PCR and found to be significantly upregulated in pancreatic cancer(*p<0.05).Conclusion:This study combined the results of single-cell sequencing and transcriptomic analysis to construct a prognostic model associated with necrosis in pancreatic cancer.This model can effectively evaluate the prognosis of pancreatic cancer patients,and the high expression of the key gene EPS8 provides a certain degree of reference for the prognosis of pancreatic cancer.