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Published on: June 9, 2017
DNA damage repair (DDR) related prognostic risk model in multiple myeloma based on single-cell and bulk sequencing
Hongxiu Liu1, Zhihua Li2, Yihua Wang3
1Second Clinical Medical College, Shanxi Medical University, Taiyuan City, China; Department of Hematology, The Second Clinical Medical College of Shanxi Medical University, Shanxi Medical University, Taiyuan, China.
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.
Insights
This study identifies DNA damage repair (DDR) gene expression as a predictor of outcomes in multiple myeloma (MM). A new risk model highlights key DDR genes for potential therapeutic targeting and improved patient stratification.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Genomic instability and rearrangements are hallmarks of multiple myeloma (MM).
- The precise origins of DNA damage and their influence on MM progression are not fully understood.
Purpose of the Study:
- To investigate the role of DNA damage repair (DDR) genes in multiple myeloma.
- To develop a prognostic model based on DDR gene expression for risk stratification and treatment guidance.
Main Methods:
- Screening of DDR genes using single-cell and bulk RNA sequencing data.
- Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis.
- Construction and validation of a prognostic nomogram model.
Main Results:
- A high DDR expression group was associated with poorer patient outcomes in both training and validation cohorts.
- DDR-related risk scores demonstrated good predictive performance.
- Differences in immune infiltration and mutation landscapes were observed between low and high DDR groups.
- PARP1, PCNA, and RAD23A were identified as key DDR-related genes in MM.
Conclusions:
- A DDR-related prognostic risk model can aid in risk stratification and inform treatment decisions for MM patients.
- Key prognostic DDR genes may serve as potential biomarkers and therapeutic targets for multiple myeloma.
