Decipherment of disulfidptosis-related mutation profile, chemosensitivity, and prognosis in diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, of which 35-40% suffers recurrence after standard chemotherapy treatment. Disulfidptosis is a novel mode of cell death, which has been found to be associated with tumor environment and prognosis in several tumors. Here, we applied transcriptome profile data of 30 types of tumors, somatic mutation data, and scRNA-seq data of DLBCL patients for analysis. Disulfidptosis-related genes (DRGs) expression was found to be widely dysregulated across different tumors, and most DRGs displayed obviously high expression in DLBCL. DRGs mutations were correlated to prognosis and chemosensitivity in DLBCL. Molecular docking analysis found the potential binding of some anti-tumor drugs and proteins encoded by mutated DRGs. Besides, scRNA-seq analysis revealed the discrepancy of DRGs expression pattern and biological pathways in diverse cell clusters. Differentially expressed genes (DEGs) between disulfidptosis-related clusters were mainly enriched in immune response and metabolism related pathways. Moreover, a novel DRGs risk score was constructed and demonstrated to be accurate for prognosis prediction in both training and validation cohorts. Pan-cancer analysis showed that DRGs score displayed wider application value in different types of tumors. Chemosensitivity analysis found that there was great discrepancy of IC50 in 86 anti-tumor drugs between low- and high-DRGs score groups, such as temozolomide and sorafenib. Overall, the novel disulfidptosis-related risk score and biomarkers have the potential to provide new insights for risk stratification and treatment recommendation in DLBCL. KEY MESSAGES: The expression of disulfidptosis-related genes (DRGs) was significantly different in 30 types of tumors, and most DRGs displayed high expression in DLBCL. DRGs mutations had the potential to predict prognosis and chemosensitivity in DLBCL. Function analysis based on sequencing datasets indicated that DRGs were closely correlated to tumor immune infiltration and metabolism reprogramming. DRGs score was found to be accurate for predicting the prognosis and chemosensitivity in DLBCL. Pan-cancer analysis revealed the prognostic value of DRGs score in different tumors.

Keywords: Chemosensitivity; Diffuse large B-cell lymphoma; Disulfidptosis; Mutation characteristics; Prognostic signature.