FTO-CHRM3 axis regulates multiple myeloma progression: a machine learning-based identification.

FTO was found to be significantly upregulated in multiple myeloma and associated with poor prognosis.

• FTO expression levels were validated in MM tissues through immunohistochemistry
• Elevated FTO expression correlated with worse clinical outcomes in MM patients
• The upregulation of FTO was identified as a consistent feature of MM progression

Machine learning and correlation analysis identified four potential FTO-associated genes in multiple myeloma.

• The four identified FTO-associated genes were CHRM3, GINS3, RRM2, and SHCBP1
• Genes were identified based on consistent expression patterns with FTO
• Both machine learning approaches and correlation analysis were used to identify these genes

Correlation and immunohistochemical analyses focused attention on the FTO-CHRM3 axis as the primary relationship of interest.

• Among the four FTO-associated genes, CHRM3 was highlighted as the most relevant through correlation analysis
• Immunohistochemistry was used to validate expression levels of both FTO and CHRM3 in MM tissues
• The FTO-CHRM3 axis was identified as a key regulatory relationship in MM progression

Functional enrichment analysis revealed that FTO and CHRM3 were involved in DNA replication and cell cycle pathways.

• Both FTO and CHRM3 were enriched in 'DNA replication' and 'cell cycle' functional categories
• These pathway associations suggest a mechanistic link between the FTO-CHRM3 axis and MM cell proliferation
• Functional enrichment analysis was used as the method to uncover these pathway involvements

The infiltration of M2 macrophages and eosinophils was altered in high FTO/CHRM3 expression groups.

• Immune infiltration analysis was used to assess the impact of FTO and CHRM3 expression on the MM immune microenvironment
• High expression groups of FTO/CHRM3 showed distinct immune cell infiltration patterns compared to low expression groups
• Specifically, M2 macrophages and eosinophils were the immune cell populations most affected

Single-cell RNA sequencing highlighted monocyte-specific expression of SLC8A1 in the calcium signaling pathway in multiple myeloma.

• scRNA-seq was used to elucidate cellular expression patterns in MM
• SLC8A1 expression was found to be specific to monocytes within the MM microenvironment
• SLC8A1's role was identified within the calcium signaling pathway, linking monocyte activity to calcium signaling dysregulation in MM

The FTO-CHRM3 axis contributes to multiple myeloma progression via calcium signaling pathway dysregulation.

• The mechanistic link between FTO-CHRM3 and MM progression was attributed to dysregulation of the calcium signaling pathway
• Exploration of this axis provides insights for targeted MM interventions
• The calcium signaling pathway connection was supported by scRNA-seq findings showing monocyte-specific SLC8A1 expression