KEY TAKEAWAYS
- The study aimed to validate the DRGs’ expression variations in DLBCL using GSE12453, GSE31312 gene expression datasets.
- Researchers observed that the DRGs play a pivotal role in DLBCL, which aided prognosis and treatment precision for improved clinical outcomes.
Diffuse large B-cell Lymphoma (DLBCL) is a malignancy characterized by large B cell proliferation, typically exhibiting a diffused growth pattern. It is the most prevalent and heterogeneous form of non-Hodgkin lymphoma. Based on its molecular and clinical features, DLBCL results in distinct biological profiles and varied responses to the current standard treatment regimens.
Disulfidptosis is a novel form of regulatory cell death triggered by disulfide stress. It is typically marked by the collapse of cytoskeleton proteins and F-actin due to the intracellular accumulation of disulfides.
Yu Wang and the team aimed to investigate and validate the expression variations of disulfide ptosis-related genes (DRGs) in DLBCL by considering 2 publicly available gene expression datasets under the study.
Researchers analyzed DRGs in DLBCL using data from GSE12453, which revealed differences in gene expression patterns between various normal B cells and DLBCL. Subsequent analysis using the data from GSE31312 identified DRGs strongly associated with prognostic outcomes, revealing 8 characteristic DRGs: CAPZB, DSTN, GYS1, IQGAP1, MYH9, NDUFA11, NDUFS1, and OXSM.
Based on these DRGs, patients with DLBCL were stratified into 3 groups, indicating that DRGs could predict prognosis and help to identify novel therapeutic candidates.
Results indicated that DRGs broadly function in mitochondrial respiration and the actin cytoskeleton. A protein-protein interaction network and a pathway heatmap illustrated these functions. Spearman correlation analysis compared the expression of these DRGs in DLBCL and normal B cells, which further highlighted the differential co-expression patterns.
About 7 DRGs exhibited significant differential expression between DLBCL and plasma cells, 10 between DLBCL and naive-B cells, and 5 between DLBCL and memory B cells.
Subsequently, total 3 distinct patient subgroups were identified based on DRG expression patterns, which were predictive of prognosis. Univariate Cox regression and LASSO regression analyses narrowed down the 24 DRGs to 8 key genes used to construct a prognostic model.
Individuals were stratified into high-risk and low-risk subgroups, with significant survival differences observed. Further clustering analysis identified 3 distinct DRG-related clusters with dynamic prognostic outcomes, emphasizing the potential of DRGs as molecular markers in DLBCL.
This study concluded that DRGs play a significant role in DLBCL. It also assessed the risk scores of individual DRGs, which allowed for more precise subcategorization of prognosis and treatment strategies for patients with DLBCL, which resulted in enhanced effectiveness of clinical implications.
The study was partially supported by a grant-in-aid for Scientific Research (C), 21K06925, titled ‘Identification of Novel ATL Biomarkers for Stratifying Disease Risk and Evaluation in Clinical Samples’, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT).
Source: https://pubmed.ncbi.nlm.nih.gov/39000261/
Wang Y, Tsukamoto Y, Hori M, et al. (2024). “Disulfidptosis: A Novel Prognostic Criterion and Potential Treatment Strategy for Diffuse Large B-Cell Lymphoma (DLBCL).” Int J Mol Sci. 2024 Jun 28;25(13):7156. doi: 10.3390/ijms25137156. PMID: 39000261; PMCID: PMC11241771.
