Abstract
Autophagy functions as a prosurvival mechanism in multiple myeloma (MM). The objective of this research was to establish an autophagy-related gene (ARG) signature for predicting the survival outcomes of MM patients with TP53 mutations. Information about MM patients with TP53 mutations was downloaded from the Gene Expression Omnibus (GEO) database. Cox proportional hazard regression was employed to determine the independent prognostic ARG and construct a risk signature. Time-dependent receiver-operating characteristic (tROC) curve analysis was used to explore the predictive accuracy of the prognostic model. A nomogram was constructed to give a more precise prediction of the probability of 5-year, 8-year and 10-year overall survival (OS). In addition, we used the CIBERSORT algorithm to explore the distribution difference of 22 immune-infiltrating cells. Three differentially expressed ARGs (CASP8, MAPK8, RB1CC1) were finally incorporated to construct the risk model. Area under the curve (AUC) values of the corresponding tROC curve for 5-year, 8-year and 10-year OS were 0.735, 0.686 and 0.662, respectively. Multiple myeloma patients were categorized into high and low-risk groups in accordance with the median threshold value (-1.724549). An ARG-based risk score model was an independent prognostic element correlated with OS, giving an hazard ratio (HR) of 3.29 (95% CI 2.35-4.60, p < 0.001). Thirteen immune infiltrating cells were found to have distribution differences between the two groups. We established a three-ARG risk signature which manifested an independent prognostic factor. The nomogram was testified to perform well in forecasting the long-term survival of TP53-mutated MM patients.
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