Comprehensive Analysis of Disulfidptosis-Related Genes in Multiple Myeloma: Implications for Prognosis and Immune Microenvironment.

INTRODUCTION

Multiple myeloma (MM) remains an incurable hematological malignancy with heterogeneous outcomes, necessitating the identification of novel prognostic markers for improved patient stratification and treatment.

METHODS

This study investigated the prognostic significance of disulfidptosis-related genes (DRGs) in MM, analyzing 1,272 samples from TCGA_MMRF and GSE4581 datasets. To explore the biological functions of key DRGs, siRNA was used to conduct in vitro experimental verification.

RESULTS

Through comprehensive bioinformatic analyses, we identified four genes (FLNA, GYS1, LRPPRC, and MYH10) significantly associated with MM prognosis. These DRGs linked the signature to disulfidptosis biology in MM. A novel four-gene signature effectively stratified patients into high-risk and low-risk groups with distinct survival outcomes, remained an independent prognostic factor, and varied significantly across disease stages. High-risk scores were associated with pathways involving mRNA processing, DNA replication, and cell-cycle progression, as well as immune shifts in neutrophil and plasma-cell fractions. Drug-sensitivity modeling showed distinct IC50 patterns between risk groups, with LRPPRC and GYS1 negatively correlated with sensitivity to selected agents. In vitro, LRPPRC knockdown in RPMI 8226 and U266 reduced viability and colony formation while increasing apoptosis, supporting the biological relevance of the signature.

CONCLUSION

This novel DRG signature not only provides a valuable tool for patient stratification but also offers insights into the biological processes driving MM progression and potential therapeutic targets.