多发性骨髓瘤（MM）是一种常见的血液恶性肿瘤，给治疗带来了巨大的挑战。胆固醇代谢失调与肿瘤发生、疾病进展和治疗抵抗有关。然而，胆固醇代谢相关基因（CMG）与 MM 预后之间的相关性仍不清楚。应用单变量 Cox 回归分析和 LASSO Cox 回归分析构建基于基因表达综合数据库的总体生存相关特征。使用三个外部数据集验证签名。在两个风险组之间进行富集分析和免疫分析。此外，还建立了适合临床应用的最佳列线图，并通过校准曲线和C指数评估其性能。总共选择了 6 个 CMG 来建立预后特征，包括 ANXA2、CHKA、NSDHL、PMVK、SCAP 和 SQLE。预后特征显示出良好的预后性能，并与几个重要的临床参数相关，包括移植数量、国际分期系统、白蛋白、β2-微球蛋白和乳酸脱氢酶水平。功能分析和免疫分析表明，代谢途径和免疫状态与风险评分相关。构建了包含签名和其他临床特征的列线图，并通过校准曲线和 C 指数验证了辨别力。我们的研究结果表明了 MM 中胆固醇代谢的潜在预后意义。预后特征的开发和验证预计将有助于预测 MM 的预后并指导精准治疗。© 2023。作者。

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.© 2023. The Author(s).