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MAMDC2-AS1 Induces Cuproptosis in Relapsed and Refractory Multiple Myeloma
Yifei Chen1, Jun Liu1, Ying Zhu1
1Department of Hematology, Jiangdu People's Hospital, Yangzhou City, China.
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.
Insights
Researchers identified MAMDC2-AS1 as a key long noncoding RNA in relapsed and refractory multiple myeloma (RRMM). This biomarker predicts patient survival and may guide new therapeutic strategies for this aggressive blood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Multiple myeloma (MM) is a plasma cell malignancy with poor prognosis in relapsed/refractory (RRMM) cases.
- Underlying mechanisms of RRMM remain incompletely understood, necessitating novel prognostic markers.
Purpose of the Study:
- To investigate the molecular mechanisms and identify prognostic biomarkers in RRMM using RNA-Seq data.
- To evaluate the potential of identified biomarkers in predicting patient survival.
Main Methods:
- Analysis of bone marrow RNA-Seq data from 557 RRMM patients (GEO database GSE24080).
- Identification of differentially expressed genes and long noncoding RNAs (lncRNAs) using LASSO Cox regression.
- Validation of findings using quantitative PCR (qPCR) and survival analysis in 57 MM patients.
Main Results:
- Significant upregulation of cuproptosis-associated genes observed in RRMM patients.
- Several lncRNAs identified as influencing copper-induced cell death and patient prognosis.
- MAMDC2-AS1 identified as a significant independent predictor of overall survival (OS) in RRMM (p < 0.01).
- High-risk group stratified by lncRNAs showed significantly worse OS (p < 0.001).
Conclusions:
- MAMDC2-AS1 is a crucial lncRNA in RRMM pathogenesis and serves as a potent prognostic biomarker.
- Targeted therapies including Bortezomib, Bosutinib, Crizotinib, and DMOG show promise for advanced RRMM.
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