Correlation of a senescence-associated gene signature with prognosis in multiple myeloma.

Abstract

7543 Background: Multiple myeloma (MM), an incurable malignancy of plasma cells, is predominantly a disease of aging. Cellular senescence, a fundamental biological process associated with aging, has been implicated in developing age-related malignancies, including MM. This study investigated the prognostic significance of senescence-associated genes within a large cohort of MM patients. Methods: Gene expression and clinical data from 1,416 MM patients were obtained from four GEO datasets (GSE24080, GSE4204, GSE57317, and GSE9782) and integrated into a unified database. Rigorous preprocessing of raw data ensured cross-platform comparability. We employed the SenMayo gene signature, a curated set of senescence-associated genes, computed as a weighted mean expression of the genes. Cox proportional hazards regression, Kaplan-Meier survival analysis, and multivariate models were used to evaluate the prognostic value of the SenMayo signature. Univaraite visualizations were plotted using the Kaplan-Meier plotter (www.kmplot.com). Clinical parameters, including gender, isotype, and molecular subtypes, were incorporated into multivariate analyses, and False Discovery Rate (FDR) correction was applied to correct for multiple hypothesis testing. Results: The SenMayo gene signature strongly correlated with overall survival (OS) in MM patients (HR = 0.6, 95% CI = 0.47–0.76, p = 1.7e-05). Patients in the low-expression group had an upper quartile survival duration of 36.1 months, compared to 57 months for those in the high-expression group. Independent validation across three datasets confirmed its prognostic value (GSE4204: HR = 0.58, 95% CI = 0.39–0.88, p = 0.0089; GSE24080: HR = 0.61, 95% CI = 0.45–0.83, p = 0.0012; GSE57317: HR = 0.25, 95% CI = 0.08–0.77, p = 0.0095). Multivariate analyses underscored the SenMayo signature as a prognostic factor, even after adjusting for established clinical parameters such as gender and isotype. Conclusions: These findings underscore the pivotal role of cellular senescence in the progression of MM. The senescence gene signature warrants further investigation to support its integration into clinical practice for improved risk stratification and informed therapeutic decision-making.