Identification and validation of prognostic genes related to centrosome amplification in multiple myeloma

Prognostic biomarkers associated with centrosome amplification-related genes (CARGs) in multiple myeloma (MM), a malignancy originating from bone marrow plasma cells, remain incompletely defined. This study aimed to identify CARG-associated prognostic genes in MM.

Transcriptome data for MM and CARGs were obtained from public databases. Initially, differentially expressed genes (DEGs) from the GSE6477 dataset were intersected with CARGs to identify candidate genes, whose biological functions were then analyzed. Regression analyses were conducted to identify prognostic genes linked to CA, from which a risk model for stratification was developed. Further analyses included nomogram construction, functional pathway analysis, immune microenvironment assessment, immunotherapy response evaluation, and drug sensitivity testing. Prognostic gene expression was validated by reverse transcription-quantitative PCR (RT-qPCR).

Forty candidate genes were identified from the intersection of 946 DEGs and 784 CARGs, which were associated with biological processes such as spindle organization. Six prognostic genes-RUVBL1, ARL2, KLHL12, ECT2, SAC3D1, and CCND1-were identified. A risk model and nomogram with superior predictive accuracy were constructed. These genes were found to influence MM pathogenesis by affecting pathways such as translation, pre-mRNA processing, retinoblastoma gene regulation in cancer, mitochondrial translation, and ribosome biogenesis. Additionally, immune cell infiltration, including naive B cells, immunotherapy responses, and drug sensitivities, particularly to CCTOO7093, were impacted by risk scores. RT-qPCR validation confirmed a significant up- regulation of these six genes in MM.

Six prognostic genes associated with CA in MM were identified, and a predictive risk model was developed, offering valuable insights for clinical prognosis and immunotherapy in MM.