Abstract
AIMS: The aims of this study were to explore the molecular mechanism of mitophagy in multiple myeloma (MM) and to develop an effective prognostic signature for the disease based on mitophagy-related genes (MRGs). METHODS: Three gene sets from the Reactome database were used to explore MRGs, following which those that were differentially expressed between MM and normal samples were investigated using the data from the Genomic Data Commons-Multiple Myeloma Research Foundation-CoMMpass Study. Mitophagy-related molecular subtypes of MM were identified and their immune infiltration, associated patient survival rates, immune checkpoint genes, and mitophagy scores were compared. Prognostic genes for MM were identified, and a prognostic model was constructed. Additionally, a nomogram was constructed using the prognostic model and prognosis-related clinical features. Finally, the drug sensitivity and correlation analyses of the subtypes were performed between the two risk groups. RESULTS: We identified two MM molecular subtypes that exhibited significant differences in mitophagy scores, associated patient survival rates, immune infiltration, and immune checkpoint genes. An MRG-based prognostic signature was constructed using six genes (TRIP13, KIF7, GPR63, CRIP2, DNTT, and HSPB8), which had high predictive prognostic value. A nomogram was constructed by screening five indicators (risk score, subtype, age, sex, and stage) that could predict the 1-, 3-, and 5-year survival probabilities of patients with MM. The two risk groups displayed significant differences in their IC(50) values of 33 drugs, such as bleomycin. Patients in the high-risk group tended to fall within Mitophagy_cluster_A. CONCLUSION: Our MRG-based signature is a promising prognostic biomarker for MM.