MAMDC2-AS1 Induces Cuproptosis in Relapsed and Refractory Multiple Myeloma

Background

Multiple myeloma is a malignant disorder involving the uncontrolled proliferation of plasma cells in the bone marrow. Prognosis remains poor for individuals with relapsed and refractory multiple myeloma (RRMM), and the underlying mechanisms are yet to be fully understood.

Methods

We collected bone marrow RNA-Seq data from a total of 557 patients with MM from the GEO database (GSE24080) for further analysis, dividing them into relapsed/refractory and control groups. Additionally, we collected bone marrow samples from 57 MM patients to validate the performed RNA-Seq data analysis.

Results

RNA-Seq analysis of patients with RRMM revealed a significant upregulation of genes associated with cuproptosis. Using the LASSO Cox regression method, several long noncoding RNAs (lncRNAs) were identified that influence copper-induced cell death. Based on these lncRNAs, patients were stratified into high-risk and low-risk groups. The high-risk group exhibited a significantly worse overall survival (OS) compared to the low-risk group, with a p-value of less than 0.001. Our statistical analysis, incorporating LASSO Cox regression, indicated that among these lncRNAs, MAMDC2-AS1 was particularly noteworthy due to its strong correlation with OS (p-value < 0.01). Further validation using qPCR and survival analysis established MAMDC2-AS1 as a strong predictor of prognosis in MM. This finding suggests that MAMDC2-AS1 can serve as a potential independent biomarker for RRMM. The qPCR data validated the RNA-Seq findings and uncovered the significance of MAMDC2-AS1 in the prognosis of this disease.

Conclusion

MAMDC2-AS1 plays a significant role in RRMM. Promisingly, Bortezomib, Bosutinib, Crizotinib, and DMOG have demonstrated promising efficacy in addressing advanced cases.