Circadian Deregulation in Multiple Myeloma: BMAL1/CLOCK Expression Patterns and Diagnostic Performance

Area of Science:

• Chronobiology and Cancer Research
• Molecular Oncology
• Biomarker Discovery

Background:

• Circadian clock disruption is implicated in cancer development and progression.
• The diagnostic significance of BMAL1 and CLOCK circadian genes in multiple myeloma (MM) is not well-established.
• Understanding circadian gene expression patterns in MM is crucial for potential diagnostic applications.

Purpose of the Study:

• To investigate the expression patterns of BMAL1 and CLOCK in multiple myeloma (MM).
• To evaluate the diagnostic relevance of BMAL1 and CLOCK in distinguishing MM patients from healthy controls.
• To explore the utility of these circadian genes as potential biomarkers for MM.

Main Methods:

• Quantification of BMAL1 and CLOCK mRNA expression using RT-qPCR in bone marrow samples from 46 MM patients and 13 controls.
• Statistical analyses including group comparisons, ROC analyses, and multivariate logistic regression.
• Application of machine-learning models (logistic regression, random forest, SVM) with cross-validation for performance assessment.

Main Results:

• BMAL1 mRNA expression was significantly higher in MM patients compared to healthy controls (p=0.016).
• BMAL1 showed moderate diagnostic performance (AUC=0.729), while CLOCK had limited discrimination (AUC=0.617).
• BMAL1 remained an independent predictor of MM in multivariate analysis; a strong correlation between BMAL1 and CLOCK expression was observed in MM.

Conclusions:

• Multiple myeloma is characterized by BMAL1 upregulation within an imbalanced BMAL1/CLOCK axis.
• The findings support a specific circadian gene expression pattern associated with MM.
• Further validation in larger cohorts is warranted to confirm the diagnostic potential of BMAL1 and CLOCK in MM.