Identification and Validation of a Prognostic Risk-Scoring Model Based on Ferroptosis-Associated Cluster in Acute Myeloid Leukemia

Abstract

Background: Emerging evidence has proven that ferroptosis plays an important role in the development of acute myeloid leukemia (AML), whereas the exact role of ferroptosis-associated genes in AML patients’ prognosis remained unclear.Materials and Methods: Gene expression profiles and corresponding clinical information of AML cases were obtained from the TCGA (TCGA-LAML), GEO (GSE71014), and TARGET databases (TARGET-AML). Patients in the TCGA cohort were well-grouped into two clusters based on ferroptosis-related genes, and differentially expressed genes were screened between the two clusters. Univariate Cox and LASSO regression analyses were applied to select prognosis-related genes for the construction of a prognostic risk-scoring model. Survival analysis was analyzed by Kaplan–Meier and receiver operator characteristic curves. Furthermore, we explored the correlation of the prognostic risk-scoring model with immune infiltration and chemotherapy response. Risk gene expression level was detected by quantitative reverse transcription polymerase chain reaction.Results: Eighteen signature genes, including ZSCAN4, ASTN1, CCL23, DLL3, EFNB3, FAM155B, FOXL1, HMX2, HRASLS, LGALS1, LHX6, MXRA5, PCDHB12, PRINS, TMEM56, TWIST1, ZFPM2, and ZNF560, were developed to construct a prognostic risk-scoring model. AML patients could be grouped into high- and low-risk groups, and low-risk patients showed better survival than high-risk patients. Area under the curve values of 1, 3, and 5 years were 0.81, 0.827, and 0.786 in the training set, respectively, indicating a good predictive efficacy. In addition, age and risk score were the independent prognostic factors after univariate and multivariate Cox regression analyses. A nomogram containing clinical factors and prognostic risk-scoring model was constructed to better estimate individual survival. Further analyses demonstrated that risk score was associated with the immune infiltration and response to chemotherapy. Our experiment data revealed that LGALS1 and TMEM56 showed notably decreased expression in AML samples than that of the normal samples.Conclusion: Our study shows that the prognostic risk-scoring model and key risk gene may provide potential prognostic biomarkers and therapeutic option for AML patients.

Identification and validation of ferroptosis related genes in prostate cancer cells under erastin exposure

“…E2F1, E2F transcription factor 1, can be one of the ferroptosis-related gene prognostic indexes (FRGPI) to predict disease-free survival (DFS) for PCa patients' radical prostatectomy, PCa patients with high FRGPI had worse DFS than patients with low FRGPI [36]. FOXL1, forkhead box L1, plays an important role in the acute myeloid leukemia prognostic model affected by ferroptosis [37]. Hence, we speculated that these TFs associated with ferroptosis also participate to the regulation of hub genes' expression to affect the ferroptosis in PCa cells.…”

A scoring system based on fusion genes to predict treatment outcomes of the non-acute promyelocytic leukemia pediatric acute myeloid leukemia

“…The R package “survival ROC” was employed to conduct a comparison of accuracy and accuracy predictions using receiver operating characteristic (ROC) curve analysis ( 26 ). The accuracy of nomogram survival was assessed by ROC curves ( 27 ). Artificial neural network was performed using the “NeuralNetTools” package.…”

Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology

“…Another study unified 18 signature genes (DLL3, EFNB3, ZSCAN4, ASTN1, FAM155B, CCL23, ZFPM2, FOXL1, HMX2, LGALS1, LHX6, PCDHB12, MXRA5, HRASLS, TMEM56, PRINS, TWIST1, and ZNF560) to develop a prognostic risk-scoring model. With the help of this model, AML patients could be grouped into high-risk and low-risk groups, with low-risk patients consistently showing better survival than high-risk patients [ 166 ]. Therefore, the development of effective activators and inhibitors targeting ferroptosis could provide new treatment strategies for AML patients.…”