Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma

Introduction 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. Material and methods Information about MM patients...

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Main Authors: Yan-Hua Zheng, Hong-Yuan Shen, Xiang Chen, Juan Feng, Guang-Xun Gao
Format: Article
Language:English
Published: Termedia Publishing House 2021-07-01
Series:Archives of Medical Science
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Online Access:https://www.archivesofmedicalscience.com/Prognostic-model-and-immune-infiltrating-cell-landscape-based-on-differentially-expressed,140293,0,2.html
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author Yan-Hua Zheng
Hong-Yuan Shen
Xiang Chen
Juan Feng
Guang-Xun Gao
author_facet Yan-Hua Zheng
Hong-Yuan Shen
Xiang Chen
Juan Feng
Guang-Xun Gao
author_sort Yan-Hua Zheng
collection DOAJ
description Introduction 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. Material and methods 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. Results 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. Conclusions 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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spelling doaj-art-6ad9657f24564fd5aefcd319d50ae1fa2025-01-27T10:44:31ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512021-07-012051619163010.5114/aoms/140293140293Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myelomaYan-Hua Zheng0https://orcid.org/0000-0002-7527-8248Hong-Yuan Shen1Xiang Chen2Juan Feng3Guang-Xun Gao4Department of Hematology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, Shaanxi, ChinaDepartment of Hematology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, Shaanxi, ChinaDepartment of Pharmacy, Daping Hospital, Third Military Medical University, Chongqing, ChinaDepartment of Hematology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, Shaanxi, ChinaDepartment of Hematology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, Shaanxi, ChinaIntroduction 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. Material and methods 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. Results 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. Conclusions 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.https://www.archivesofmedicalscience.com/Prognostic-model-and-immune-infiltrating-cell-landscape-based-on-differentially-expressed,140293,0,2.htmlmultiple myelomaautophagyprognosisrisk signaturetp53 mutationimmune-infiltrating cell
spellingShingle Yan-Hua Zheng
Hong-Yuan Shen
Xiang Chen
Juan Feng
Guang-Xun Gao
Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma
Archives of Medical Science
multiple myeloma
autophagy
prognosis
risk signature
tp53 mutation
immune-infiltrating cell
title Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma
title_full Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma
title_fullStr Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma
title_full_unstemmed Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma
title_short Prognostic model and immune-infiltrating cell landscape based on differentially expressed autophagy-related genes in TP53-mutated multiple myeloma
title_sort prognostic model and immune infiltrating cell landscape based on differentially expressed autophagy related genes in tp53 mutated multiple myeloma
topic multiple myeloma
autophagy
prognosis
risk signature
tp53 mutation
immune-infiltrating cell
url https://www.archivesofmedicalscience.com/Prognostic-model-and-immune-infiltrating-cell-landscape-based-on-differentially-expressed,140293,0,2.html
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AT xiangchen prognosticmodelandimmuneinfiltratingcelllandscapebasedondifferentiallyexpressedautophagyrelatedgenesintp53mutatedmultiplemyeloma
AT juanfeng prognosticmodelandimmuneinfiltratingcelllandscapebasedondifferentiallyexpressedautophagyrelatedgenesintp53mutatedmultiplemyeloma
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