Integrative analysis of an endoplasmic reticulum stress-related signature in multiple myeloma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Multiple myeloma (MM) is an incurable plasma cell malignancy.
• MM cells exhibit high endoplasmic reticulum stress (ERS) and rely on its response for survival.
• Identifying ERS-related molecular signatures is crucial for MM diagnosis and treatment.

Purpose of the Study:

• To identify an ERS-related gene signature for multiple myeloma (MM).
• To evaluate the diagnostic value of the identified ERS-related genes in MM.
• To explore potential therapeutic targets and molecular interactions associated with ERS in MM.

Main Methods:

• Downloaded and analyzed three MM datasets from the Gene Expression Omnibus database.
• Identified ERS-related differentially expressed genes (ERDEGs) and performed Gene Ontology enrichment analysis.
• Constructed protein-protein interaction, transcription factor-mRNA, miRNA-mRNA, and drug-mRNA networks.
• Assessed immune cell infiltration and diagnostic value using receiver operating characteristic analyses.
• Validated ERDEG expression using quantitative polymerase chain reaction (qPCR).

Main Results:

• Identified a signature of nine ERDEGs in MM.
• ERDEGs are implicated in endoplasmic reticulum membrane functions.
• Established interaction networks revealing potential molecular partners and drug targets for the ERDEGs.
• Demonstrated significant correlations between ERDEGs and immune cell infiltration.
• Confirmed good diagnostic values for these potential MM biomarkers.
• Observed differential expression of ERDEGs in MM cells compared to healthy donors.

Conclusions:

• The nine identified ERS-related genes (CR2, DHCR7, DNAJC3, KDELR2, LPL, OSBPL3, PINK1, VCAM1, XBP1) are potential biomarkers for MM.
• This gene signature holds promise for advancing the clinical diagnosis and treatment of multiple myeloma.
• Further research into these ERDEGs could uncover novel therapeutic strategies for MM.