Identification of a cholesterol metabolism-related prognostic signature for multiple myeloma

Abstract Multiple myeloma (MM) is a prevalent hematological malignancy that poses significant challenges for treatment. Dysregulated cholesterol metabolism has been linked to tumorigenesis, disease progression, and therapy resistance. However, the correlation between cholesterol metabolism-related genes (CMGs) and the prognosis of MM remains unclear. Univariate Cox regression analysis and LASSO Cox regression analysis were applied to construct an overall survival-related signature based on the Gene Expression Omnibus database. The signature was validated using three external datasets. Enrichment analysis and immune analysis were performed between two risk groups. Furthermore, an optimal nomogram was established for clinical application, and its performance was assessed by the calibration curve and C-index. A total of 6 CMGs were selected to establish the prognostic signature, including ANXA2, CHKA, NSDHL, PMVK, SCAP and SQLE. The prognostic signature demonstrated good prognostic performance and correlated with several important clinical parameters, including number of transplants, International Staging System, albumin, beta2-Microglobulin and lactate dehydrogenase levels. The function analysis and immune analysis revealed that the metabolic pathways and immunologic status were associated with risk score. The nomogram incorporating the signature along with other clinical characteristics was constructed and the discrimination was verified by the calibration curve and C-index. Our findings indicated the potential prognostic connotation of cholesterol metabolism in MM. The development and validation of the prognostic signature is expected to aid in predicting prognosis and guiding precision treatment for MM.