A neutrophil extracellular trap-related risk score predicts prognosis and characterizes the tumor microenvironment in
Zhijia Zhao1, Yuan Huo2, Yufeng Du1,3
1Liaoning Key Laboratory of Hematopoietic Stem Cell Transplantation and Translational Medicine, Department of Hematology, Liaoning Medical Center for Hematopoietic Stem Cell Transplantation, The Second Hospital of Dalian Medical University, Dalian, 116023, China.
Abstract:
Multiple myeloma (MM) is a distinguished hematologic malignancy, with existing studies elucidating its interaction with neutrophil extracellular traps (NETs), which may potentially facilitate tumor growth. However, systematic investigations into the role of NETs in MM remain limited. Utilizing the single-cell dataset GSE223060, we discerned active NET cell subgroups, namely neutrophils, monocytes, and macrophages. A transcriptional trajectory was subsequently constructed to comprehend the progression of MM. Following this, an analysis of cellular communication in MM was conducted with a particular emphasis on neutrophils, revealing an augmentation in interactions albeit with diminished strength, alongside abnormal communication links between neutrophils and NK cells within MM samples. Through the intersection of differentially expressed genes (DEGs) between NET active/inactive cells and MM versus healthy samples, a total of 316 genes were identified. This led to the development of a 13-gene risk model for prognostic prediction based on overall survival, utilizing transcriptomics dataset GSE136337. The high-risk group manifested altered immune infiltration and heightened sensitivity to chemotherapy. A constructed nomogram for predicting survival probabilities demonstrated encouraging AUCs for 1, 3, and 5-year survival predictions. Collectively, our findings unveil a novel NET-related prognostic signature for MM, thereby providing a potential avenue for therapeutic exploration.
Insights
This study reveals neutrophil extracellular traps (NETs) play a role in multiple myeloma (MM) progression. A new 13-gene signature predicts MM survival and chemotherapy response, offering therapeutic insights.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Multiple myeloma (MM) is a hematologic malignancy where neutrophil extracellular traps (NETs) may promote tumor growth.
- Systematic investigation into the specific role of NETs in MM pathogenesis is limited.
Purpose of the Study:
- To investigate the role of NETs in MM progression using single-cell data.
- To identify NET-related molecular signatures for MM prognosis and therapeutic targeting.
Main Methods:
- Analysis of single-cell RNA sequencing data (GSE223060) to identify NET-active cell populations and construct transcriptional trajectories.
- Cellular communication analysis focusing on neutrophils in MM samples.
- Differential gene expression analysis and development of a prognostic risk model using transcriptomics data (GSE136337).
Main Results:
- Identified neutrophils, monocytes, and macrophages as active NET cells in MM.
- Observed altered neutrophil-NK cell communication and increased but weaker interactions involving neutrophils in MM.
- Developed a 13-gene prognostic signature; high-risk group showed altered immune infiltration and increased chemotherapy sensitivity.
- A nomogram demonstrated good predictive accuracy for 1, 3, and 5-year survival.
Conclusions:
- A novel NET-related prognostic signature for multiple myeloma has been identified.
- This signature may aid in predicting patient survival and response to chemotherapy.
- Findings suggest NETs as a potential therapeutic target in MM.
More Related Videos
09:59A High-throughput Assay to Assess and Quantify Neutrophil Extracellular Trap Formation
Published on: January 29, 2019
11:32Real-Time, High-Throughput Microscopic Quantification of Human Neutrophil Extracellular Trap Release and Assessing the Pharmacology of Antagonists
Published on: October 18, 2024
