Cuproptosis-Related Gene Signature Contributes to Prognostic Prediction and Immunosuppression in Multiple Myeloma.

Abstract

Cuproptosis is a type of programmed cell death triggered by accumulation of intracellular copper which was considered closely related to tumor progression. The study of cuproptosis in multiple myeloma (MM) is however limited. To determine the prognostic significance of cuproptosis-related gene signature in MM, we interrogated gene expression and overall survival with other available clinical variables from public datasets. Four cuproptosis-related genes were included to establish a prognostic survival model by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, which showed a good performance on prognosis prediction in both training and validation cohorts. Patients with higher cuproptosis-related risk score (CRRS) exhibited worse prognosis compared with lower risk score. Survival prediction capacity and clinical benefit were elevated after integrating CRRS to existing prognostic stratification system (International Staging System, ISS or Revised International Staging System, RISS) both on 3-year and 5-year survival. Based on CRRS groups, functional enrichment analysis and immune infiltration in bone marrow microenvironment revealed correlation between CRRS and immunosuppression. In conclusion, our study found that cuproptosis-related gene signature is an independent poor prognostic factor and functions negatively on immune microenvironment, which provides another perspective on prognosis assessment and immunotherapy strategy in MM.