Page 130 - GPD-3-4

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
A new gene signature associated with pyroptosis

for identifying high-risk myeloma patients

1,2
Yaner Wang , Qi Wang , Zhenqian Huang , and Xinliang Mao 1,2,3 *
3
2
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

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
*Corresponding author: genes – CASP3, CHMP2A, CHMP3, CHMP6, GZMB, CASP8, NOD2, PLCG1, and FOXO3 –
Xinliang Mao
(xinliangmao@gzhmu.edu.cn) 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
Citation: Wang Y, Wang Q, same prognostic model was also successfully constructed in the internal test cohort.
Huang Z, Mao X. A new gene
signature associated with pyroptosis Thus, a prognostic risk model for clinically predicting the survival rate of MM patients
for identifying high-risk myeloma was established. Single-sample gene set enrichment analysis was employed to
patients. Gene Protein Dis. analyze immune infiltrating cells and immune-related pathways between two risk
2024;3(4):4534.
doi: 10.36922/gpd.4534 groups. Moreover, the mRNA expression levels of the prognostic risk signature genes
were confirmed by quantitative reverse-transcription polymerase chain reaction in
Received: August 15, 2024
MM cells treated with the pyroptosis-inducing agent etoposide. In conclusion, we
Accepted: December 3, 2024 identified a 9-PRG signature that enables effective stratification of MM patients and
Published Online: December 17, serves as an independent prognostic marker. These findings underscore the need for
2024 further exploration of pyroptosis in MM therapy.
Copyright: © 2024 Author(s).
This is an Open-Access article
distributed under the terms of the Keywords: Multiple myeloma; Pyroptosis; Signature gene; Prognosis
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited. 1. Introduction
Publisher’s Note: AccScience Multiple Myeloma (MM) is a plasma cell malignancy more commonly affecting
Publishing remains neutral with the elderly individuals. The average age at diagnosis of MM patients is 69 years,
1
regard to jurisdictional claims in
published maps and institutional according to the annual report of American Cancer Society website (Key Statistics
affiliations. About MM). The annual global incidence is approximately 2/100,000 people, making

Volume 3 Issue 4 (2024) 1 doi: 10.36922/gpd.4534