Prognostic value assessment and in vitro validation of mitochondria-ferroptosis-related genes in multiple myeloma.

Multiple myeloma (MM) is a malignant plasma cell tumor. Mitochondria-related genes (MRGs) are significant inducers of ferroptosis. However, research on the involvement of mitochondria-ferroptosis-related genes (MFRGs) in the MM is relatively scarce, and further identification of key genes associated with MFRGs in MM treatment is needed. In this study, transcriptomic data and related genes were initially downloaded from public databases and literature. Subsequently, candidate genes were obtained by intersecting the differential expression genes (DEGs) from MM and control groups, and MFRGs. Through regression analyses, clinically relevant genomic signatures were delineated, culminating in the development of a predictive algorithm. An independent prognostic analysis was conducted, followed by the creation of a nomogram. Subsequently, these prognostic genes were studied from various aspects. Finally, the transcriptional abundance of predictive biomarkers was experimentally validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR). The intersection of DEGs and MFRGs yielded 15 candidate genes. Then, GPR15, NLRP7, ZNF208, PRDM13, and CRIM1 were identified as prognostic genes. The prognostic model constructed using these prognostic genes was confirmed to be robust. The 2 independent prognostic factors (risk score and age) were determined, and the constructed nomogram provided an excellent predictive model. Then, risk score and activated dendritic cells were found to be significantly negatively correlated (cor = -0.43, p < 0.05). Additionally, GPR15 was positively associated with M2 macrophages (cor = 0.34, p < 0.05), while NLRP7 and PRDM13 were negatively associated with activated dendritic cells (cor = -0.34, p < 0.05; cor = -0.40, p < 0.05). There were 3 significantly different immune cells, 31 significantly immune checkpoint genes, and 11 significantly different immune checkpoints (p < 0.05). ZNF208, PRDM13, and CPIM1 were all mainly enriched in ribosome-related pathways. Finally, 86 potential drugs for the treatment of MM were discovered, such as shikonin. RT-qPCR results showed that NLRP7 and PRDM13 were significantly upregulated in MM group, while GPR15 and CRIM1 were significantly downregulated in MM group (p < 0.05). In this study, 5 MFRGs were identified as prognostic genes (GPR15, NLRP7, ZNF208, PRDM13, and CRIM1) for MM, which provide reference significance for the prognosis of MM.