The ER stress related gene panel guide the prognosis and chemosensitivity in acute myeloid leukemia

Abstract

Background Acute myeloid leukemia possess high heterogeneity and current European Leukemia Net (ELN) risk stratification system cannot be applicable to all AML patients and needs about 3 weeks testing cycle. The aim of this study was to develop a applicable prognostic tool that may overcome the above shortcomings. Methods We used AML patients collected in clinic and TCGA database to explore the role of ER stress in response to chemotherapy. Patients from the TCGA database were used as the training cohort, and two GEO datasets were used as external validation cohorts. Univariate /multivariate COX and LASSO regression was exemplified to establish the prognostic model. Kaplan-Meier and time-dependent ROC were used to assess and compare the efficiency of the model with ELN stratification and other models. R package "pRRophetic" was utilized to assess drug sensitivity. Results In the training cohort, we selected 5 ER stress-related genes to predict chemosensitivity and establish the ERS-5 prognostic model. The model successfully predicted the overall survival of patients; p < 0.0001, HR = 4.86 (2.79–8.44); AUC = 0.83. The model was verified in validation cohorts and could further stratify the risk of various AML subgroups. It also complemented the ability of ELN to predict the response of patients with AML to main chemotherapeutic drugs. Finally, a “ERS-5” risk score was construced by the nomogram based on the ERS-5 model and age. Conclusions The ERS-5 model allowed more rapid (about 3 hours) and accurate risk stratification and complemented the ability of ELN to assess chemosensitivity.