RNA-Sequencing-Based Transcriptomic Score with Prognostic and Theranostic Values in Multiple Myeloma

Area of Science:

• Hematological Oncology
• Genomics
• Biomedical Research

Background:

• Multiple myeloma (MM) is a prevalent hematological cancer driven by malignant plasma cell proliferation.
• Genome-wide expression profiling (GEP) using DNA microarrays has significantly advanced MM research and clinical applications.
• GEP in MM aids in patient stratification, risk assessment, target identification, and understanding treatment resistance.

Purpose of the Study:

• To develop and validate a prognostic gene risk score for newly diagnosed multiple myeloma patients.
• To identify key biological pathways and gene expression patterns associated with high-risk MM.
• To explore the correlation of the gene risk score with somatic mutations and targeted therapy responses.

Main Methods:

• Construction of a 267-gene risk score using RNA-sequencing (RNA-seq) data.
• Validation of the risk score in two independent cohorts of newly diagnosed MM patients (n=674 and n=76) treated with high-dose Melphalan and autologous stem cell transplantation.
• Analysis of gene expression pathways, somatic mutation profiles, and targeted treatment responses.

Main Results:

• The RNA-seq-based gene risk score demonstrated significant prognostic value in both independent cohorts.
• High-risk patients exhibited expression of genes in pathways including interferon response, cell proliferation, hypoxia, IL-6 signaling, stem cell genes, MYC, and epigenetic deregulation.
• The risk score correlated with specific MM somatic mutations and responses to targeted agents like EZH2, MELK, and Aurora kinase inhibitors.

Conclusions:

• The developed gene risk score is a valuable prognostic tool for newly diagnosed MM patients.
• Gene expression profiles in high-risk MM provide insights into disease pathophysiology and potential therapeutic vulnerabilities.
• This RNA-seq-based approach supports the development of precision medicine strategies for multiple myeloma treatment.