Transcriptome Analysis Identifies Functional and Prognostic Hypoxia-Associated Genes in Multiple Myeloma

Area of Science:

• Oncology
• Molecular Biology
• Biomedical Research

Background:

• Multiple myeloma (MM) is an incurable B-cell malignancy driven by neoplastic plasma cell accumulation in the bone marrow.
• Emerging evidence suggests hypoxia significantly promotes MM progression, yet the precise molecular mechanisms remain largely unknown.

Purpose of the Study:

• To investigate the role of hypoxia in multiple myeloma.
• To identify hypoxia-associated genes (HAGs) involved in MM progression and their association with patient survival.

Main Methods:

• Gene expression profiling of MM cell lines under hypoxia.
• Analysis of the MMRF CoMMpass cohort for differentially expressed HAGs.
• Validation of HAG expression in patient bone marrow samples and single-cell RNA sequencing data.

Main Results:

• Identified 17 HAGs in MM cell lines and 92 in MM patients, with 9 common HAGs (ADM, BNIP3L, EGLN1, FAM162A, HMOX1, PDK1, PLOD1, STAT5B, TFRC).
• Eight of these HAGs significantly correlated with overall MM patient survival, and six with first-year survival.
• Confirmed severe hypoxia in the bone marrow microenvironment of MM patients compared to healthy individuals.

Conclusions:

• The identified HAGs are crucial indicators of hypoxia in MM.
• These findings offer potential therapeutic targets and prognostic biomarkers for multiple myeloma patients.