DNA damage repair (DDR) related prognostic risk model in multiple myeloma based on single-cell and bulk sequencing

Abstract

Genomic rearrangements and instability are key pathological features of multiple myeloma (MM). However, the origins of DNA damage in MM and its impact on disease progression remain incompletely understood. Here, we screened DNA damage repair (DDR) genes from single-cell RNA sequencing and bulkRNA-seq datasets using WGCNA and differential expression analysis. A prognostic model was constructed, demonstrating that patients in high DDR expression group had poor outcomes in both the training and validation cohorts. The nomogram also indicated that DDR-related risk scores had good predictive performance. Then, the differences of immune infiltration and mutation landscape between low and high DDR group were investigated. PARP1, PCNA, and RAD23A were identified as key DDR-related genes in MM. Additionally, we explored the drug sensitivity and potential molecular mechanisms associated with each key gene. Altogether, the DDR-related prognostic risk model in MM may facilitate risk stratification and guide treatment decisions, with key prognostic genes might potentially serving as biomarkers and therapeutic targets.