Leveraging a disulfidptosis-based signature to characterize heterogeneity and optimize treatment in multiple myeloma

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

Disulfidptosis is an emerging type of programmed cell death related to ROS accumulation and aberrant disulfide bond formation. Multiple myeloma (MM) the second most prevalent hematologic malignancy characterized by a high synthesis rate bond-rich proteins chronic oxidative stress. However, relationship between disulfidptosis MM still unclear. Using non-negative matrix factorization lasso algorithm, we constructed disulfidptosis-associated subtypes prognostic model on GEO dataset. We further explored genetic mutation mapping, protein-protein interactions, functional enrichment, drug sensitivity, prediction, immune infiltration analysis among risk subgroups. To improve clinical benefits, combined scores metrics build nomogram. Finally, in vitro experiments examined expression patterns disulfidptosis-related genes (DRGs) MM. By cluster analysis, obtained three with C2 having worse prognosis than C3. Consistently, exhibited significantly lower sensitivity doxorubicin lenalidomide, as well higher propensity for T-cell depletion non-responsive state immunotherapy. Similarly, subsequent model, high-scoring group had probability dysfunction, immunotherapy resistance, cancer self-renewal. DRGs were widely mutated cancers. Subtypes subgroups differed metabolism p53 signaling pathway. identified eight differentially expressed targets against Then 27 drugs targeting high-risk predicted. Based genes, miRNA TF regulatory networks. The nomogram ISS, age, score showed good predictive performance. qRT-PCR lines specimens provided support modeling. Our research reveals value provides new perspectives identifying heterogeneity therapeutic targets.

Language: Английский

Gaudichaudion H Inhibits KRAS-mutant Pancreatic Cancer Cell Growth through Interfering PDEδ-KRAS Interaction

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111529 - 111529

Published: April 1, 2025

Language: Английский

Disulfidptosis in tumor progression

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 28, 2025

Abstract Disulfidptosis, a regulated cell death modality driven by the cystine transporter solute carrier family 7 member 11 (SLC7A11), is characterized actin cytoskeleton collapse under glucose starvation. This review systematically elucidates pivotal role of disulfidptosis in tumor metabolic reprogramming, with focus on its molecular mechanisms and distinctions from other pathways. The core include SLC7A11-mediated overload NRF2/c-Myc-regulated pentose phosphate pathway activation. By integrating multiomics data single-cell transcriptomics, we comprehensively decipher heterogeneous expression patterns disulfidptosis-related genes (DRGs) their dynamic interplay immune microenvironment remodeling. Furthermore, coexpression networks DRGs long noncoding RNAs (DRLs) offer novel insights into diagnosis, prognosis, targeted therapy. Therapeutically, SLC7A11 inhibitors (e.g., HG106) BAY-876) demonstrate efficacy exploiting vulnerabilities, whereas natural compounds synergizing checkpoint blockade provide strategies to counteract immunosuppressive microenvironments. Through interdisciplinary collaboration clinical translation, research holds transformative potential redefining precision oncology.

Language: Английский