AccScience Publishing / GPD / Volume 3 / Issue 4 / 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.
References
  1. Rajkumar SV. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(7):719-734. doi: 10.1002/ajh.24402

 

  1. Kazandjian D. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676-681. doi: 10.1053/j.seminoncol.2016.11.004

 

  1. Palumbo A, Anderson K. Multiple myeloma. New Engl J Med. 2011;364(11):1046-1060. doi: 10.1056/NEJMra1011442

 

  1. Puig N, Paiva B, Lasa M, et al. Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis. Leukemia. 2019;33(5):1256-1267. doi: 10.1038/s41375-018-0308-5

 

  1. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): A randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38. doi: 10.1016/s0140-6736(19)31240-1

 

  1. Walker BA, Morgan GJ. The genomic features associated with high-risk multiple myeloma. Oncotarget. 2018;9(84): 35478-35479. doi: 10.18632/oncotarget.26269

 

  1. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):1086-1107. doi: 10.1002/ajh.26590

 

  1. Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122-1128. doi: 10.1038/leu.2013.313

 

  1. van de Donk N, Pawlyn C, Yong KL. Multiple myeloma. Lancet. 2021;397(10272):410-427. doi: 10.1016/S0140-6736(21)00135-5

 

  1. Farhana A, Lappin SL. Biochemistry, lactate dehydrogenase. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2023.

 

  1. Liang JP, He YM, Cui YL, et al. Proteasomal inhibitors induce myeloma cell pyroptosis via the BAX/GSDME pathway. Acta Pharmacol Sin. 2023;44(7):1464-1474. doi: 10.1038/s41401-023-01060-3

 

  1. Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev. 2015;265(1):130-142. doi: 10.1111/imr.12287

 

  1. Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660-665. doi: 10.1038/nature15514

 

  1. Chen X, He WT, Hu L, et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res. 2016;26(9):1007-1020. doi: 10.1038/cr.2016.100

 

  1. Ding J, Wang K, Liu W, et al. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016;535(7610):111-116. doi: 10.1038/nature18590

 

  1. Li T, Zheng G, Li B, Tang L. Pyroptosis: A promising therapeutic target for noninfectious diseases. Cell Prolif. 2021;54(11):e13137. doi: 10.1111/cpr.13137

 

  1. Man SM. Inflammasomes in the gastrointestinal tract: Infection, cancer and gut microbiota homeostasis. Nature Rev Gastroenterol Hepatol. 2018;15(12):721-737. doi: 10.1038/s41575-018-0054-1

 

  1. Fang Y, Tian S, Pan Y, et al. Pyroptosis: A new frontier in cancer. Biomed Pharmacother. 2020;121:109595. doi: 10.1016/j.biopha.2019.109595

 

  1. Xia X, Wang X, Cheng Z, et al. The role of pyroptosis in cancer: Pro-cancer or pro-“host”? Cell Death Dis. 2019;10(9):650. doi: 10.1038/s41419-019-1883-8

 

  1. Shi M, Tang C, Wu JX, et al. Mass spectrometry detects sphingolipid metabolites for discovery of new strategy for cancer therapy from the aspect of programmed cell death. Metabolites. 2023;13(7):867. doi: 10.3390/metabo13070867

 

  1. Rao Z, Zhu Y, Yang P, et al. Pyroptosis in inflammatory diseases and cancer. Theranostics. 2022;12(9):4310-4329. doi: 10.7150/thno.71086

 

  1. He Y, Jiang S, Cui Y, et al. Induction of IFIT1/IFIT3 and inhibition of Bcl-2 orchestrate the treatment of myeloma and leukemia via pyroptosis. Cancer Lett. 2024;588:216797. doi: 10.1016/j.canlet.2024.216797

 

  1. Chen LL, Chen X, Choi H, et al. Exploiting antitumor immunity to overcome relapse and improve remission duration. Cancer Immunol Immunother. 2012;61(7):1113-1124. doi: 10.1007/s00262-011-1185-1

 

  1. Guner A, Kim HI. Biomarkers for evaluating the inflammation status in patients with cancer. J Gastric Cancer. 2019;19(3):254-277. doi: 10.5230/jgc.2019.19.e29

 

  1. Yu P, Zhang X, Liu N, Tang L, Peng C, Chen X. Pyroptosis: Mechanisms and diseases. Signal Transduct Target Ther. 2021;6(1):128. doi: 10.1038/s41392-021-00507-5

 

  1. Wang H, Shao R, Lu S, et al. Integrative analysis of a pyroptosis-related signature of clinical and biological value in multiple myeloma. Front Oncol. 2022;12:845074. doi: 10.3389/fonc.2022.845074

 

  1. Zhang C, Wu S, Chen B. A novel prognostic model based on pyroptosis-related genes for multiple myeloma. BMC Med Genomics. 2023;16(1):32. doi: 10.1186/s12920-023-01455-5

 

  1. Li C, Liang H, Bian S, Hou X, Ma Y. Construction of a prognosis model of the pyroptosis-related gene in multiple myeloma and screening of core genes. ACS Omega. 2022;7(38):34608-34620. doi: 10.1021/acsomega.2c04212

 

  1. Yuan C, Yuan M, Chen M, et al. Prognostic implication of a novel metabolism-related gene signature in hepatocellular carcinoma. Front Oncol. 2021;11:666199. doi: 10.3389/fonc.2021.666199

 

  1. Ye J, She X, Liu Z, et al. Eukaryotic initiation factor 4A-3: A review of its physiological role and involvement in oncogenesis. Front Oncol. 2021;11:712045. doi: 10.3389/fonc.2021.712045

 

  1. Chen W, Zhang W, Zhou T, Cai J, Yu Z, Wu Z. A newly defined pyroptosis-related gene signature for the prognosis of bladder cancer. Int J Gen Med. 2021;14:8109-8120. doi: 10.2147/ijgm.S337735

 

  1. Du H, Xie S, Guo W, et al. Development and validation of an autophagy-related prognostic signature in esophageal cancer. Ann Transl Med. 2021;9(4):317. doi: 10.21037/atm-20-4541

 

  1. Yang Y, Wu G, Li Q, et al. Angiogenesis-related immune signatures correlate with prognosis, tumor microenvironment, and therapeutic sensitivity in hepatocellular carcinoma. Front Mol Biosci. 2021;8:690206. doi: 10.3389/fmolb.2021.690206

 

  1. Fang Y, Huang S, Han L, Wang S, Xiong B. Comprehensive analysis of peritoneal metastasis sequencing data to identify LINC00924 as a Prognostic biomarker in gastric cancer. Cancer Manag Res. 2021;13:5599-5611. doi: 10.2147/cmar.S318704

 

  1. Yuan M, Wang Y, Sun Q, et al. Identification of a nine immune-related lncRNA signature as a novel diagnostic biomarker for hepatocellular carcinoma. Biomed Res Int. 2021;2021:9798231. doi: 10.1155/2021/9798231

 

  1. Dai Y, Qiang W, Lin K, Gui Y, Lan X, Wang D. An immune-related gene signature for predicting survival and immunotherapy efficacy in hepatocellular carcinoma. Cancer Immunol Immunother. 2021;70(4):967-979. doi: 10.1007/s00262-020-02743-0

 

  1. Zhao WJ, Ou GY, Lin WW. Integrative analysis of neuregulin family members-related tumor microenvironment for predicting the prognosis in gliomas. Front Immunol. 2021;12:682415. doi: 10.3389/fimmu.2021.682415

 

  1. Fu J, Li K, Zhang W, et al. Large-scale public data reuse to model immunotherapy response and resistance. Genome Med. 2020;12(1):21. doi: 10.1186/s13073-020-0721-z

 

  1. Jiang P, Gu S, Pan D, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nature Med. 2018;24(10):1550-1558. doi: 10.1038/s41591-018-0136-1

 

  1. Wang Y, Gao W, Shi X, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547(7661):99-103. doi: 10.1038/nature22393

 

  1. Shi J, Gao W, Shao F. Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 2017;42(4):245-254. doi: 10.1016/j.tibs.2016.10.004

 

  1. Ju X, Yang Z, Zhang H, Wang Q. Role of pyroptosis in cancer cells and clinical applications. Biochimie. 2021;185:78-86. doi: 10.1016/j.biochi.2021.03.007

 

  1. Verma R, Marchese A. The endosomal sorting complex required for transport pathway mediates chemokine receptor CXCR4-promoted lysosomal degradation of the mammalian target of rapamycin antagonist DEPTOR. J Biol Chem. 2015;290(11):6810-6824. doi: 10.1074/jbc.M114.606699

 

  1. Raab M, Gentili M, de Belly H, et al. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science. 2016;352(6283):359-362. doi: 10.1126/science.aad7611

 

  1. Tian Z, Tong X, Sheng G, et al. Printable magnesium ion quasi-solid-state asymmetric supercapacitors for flexible solar-charging integrated units. Nat Commun. 2019;10(1):4913. doi: 10.1038/s41467-019-12900-4

 

  1. Zhang S, Li X, Zhang X, Zhang S, Tang C, Kuang W. The pyroptosis-related gene signature predicts the prognosis of hepatocellular carcinoma. Front Mol Biosci. 2021;8:781427. doi: 10.3389/fmolb.2021.781427
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