AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.4534
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ORIGINAL RESEARCH ARTICLE

A new gene signature associated with pyroptosis for identifying high-risk myeloma patients

Yaner Wang1,2 ,  Qi Wang2 ,  Zhenqian Huang3 ,  Xinliang Mao1,2,3*
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1 Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
2 Guangdong and Guangzhou Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China
3 Department of Hematology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
GPD 2024, 3(4), 4534 https://doi.org/10.36922/gpd.4534
Submitted: 15 August 2024 | Accepted: 3 December 2024 | Published: 17 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Multiple myeloma (MM) is a complicated hematologic malignancy of plasma cells. However, the existing stratification systems cannot accurately predict the prognosis of MM. This study aims to evaluate the role of pyroptosis in identifying high-risk MM patients. RNA expression profiles were obtained from the Cancer Genome Atlas-MMRF CoMMpass and GTEx databases, which were treated as MM cases and controls, respectively. By applying univariate Cox regression analysis and consensus clustering, 20 pyroptosis-related genes (PRGs) were initially identified to effectively stratify MM patients into two distinct subgroups. To identify prognostic gene signature, a stepwise LASSO regression analysis was conducted following by univariate and multivariate Cox regression analyses. We identified a set of signature genes – CASP3, CHMP2A, CHMP3, CHMP6, GZMB, CASP8, NOD2, PLCG1, and FOXO3 – that could significantly distinguish MM patients based on overall survival. We further identified that the risk score can serve as an independent prognostic indicator. The same prognostic model was also successfully constructed in the internal test cohort. Thus, a prognostic risk model for clinically predicting the survival rate of MM patients was established. Single-sample gene set enrichment analysis was employed to analyze immune infiltrating cells and immune-related pathways between two risk groups. Moreover, the mRNA expression levels of the prognostic risk signature genes were confirmed by quantitative reverse-transcription polymerase chain reaction in MM cells treated with the pyroptosis-inducing agent etoposide. In conclusion, we identified a 9-PRG signature that enables effective stratification of MM patients and serves as an independent prognostic marker. These findings underscore the need for further exploration of pyroptosis in MM therapy.

Keywords
Multiple myeloma
Pyroptosis
Signature gene
Prognosis
Funding
This project was partly supported by the National Key Research and Development Program of China (#2022YFC2705003), National Natural Science Foundation of China (#82170176), and Guangzhou Medical University Discipline Construction Funds (Basic Medicine) (#JCXKJS2022A05).
Conflict of interest
Xinliang Mao is the Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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