Deconvolution of Bulk Gene Expression Profiles with Single-Cell Transcriptomics to Develop a Cell Type
Chengguqiu Dai1, Mengya Chen1, Chaolong Wang1
1Department of Epidemiology and Biostatistics, Key Laboratory for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Frontiers in Cell and Developmental Biology
|December 6, 2021
Summary
This study introduces a novel prognostic model for adult Acute Myeloid Leukemia (AML) based on cell type compositions (CTCs). The CTC score, comprising GMP-like, HSC-like, and T cells, effectively predicts patient mortality risk and aids in personalized treatment planning.
Area of Science:
- Hematology
- Oncology
- Bioinformatics
Background:
- Acute Myeloid Leukemia (AML) is a rapidly progressing hematologic cancer with a poor prognosis.
- Current AML prognostic models primarily rely on genetic abnormalities, neglecting cell type compositions (CTCs).
- There is a need for novel prognostic markers to improve AML patient stratification and treatment strategies.
Purpose of the Study:
- To develop and validate a novel prognostic model for adult AML based on peripheral blood and bone marrow cell type compositions (CTCs).
- To evaluate the prognostic performance of the developed CTC score against existing gene expression-based scores.
Main Methods:
- Utilized the CIBERSORT algorithm to estimate CTCs from public AML datasets (GSE6891, TCGA-LAML) using a custom AML single-cell RNA sequencing reference.
- Developed a CTC-based prognostic model, the CTC score, using least absolute shrinkage and selection operator (LASSO) Cox regression.
- Validated the CTC score's significance and compared its performance with the 17-gene leukemic stem cell score (LSC17) and AML prognostic score (APS).
Main Results:
- The CTC score, comprising GMP-like, HSC-like, and T cells, significantly stratified AML patients into high and low mortality risk groups.
- High CTC score was associated with a 1.57-fold and 2.32-fold higher overall mortality risk in training and validation sets, respectively.
- The CTC score demonstrated comparable performance to LSC17 and APS, providing independent and additional prognostic information.
Conclusions:
- The CTC score serves as a powerful and independent prognostic marker for adult AML.
- This novel CTC-based model has significant potential to assist clinicians in formulating individualized treatment plans for AML patients.
- Incorporating cell type composition into prognostic models offers a promising avenue for improving AML patient management.
