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Article Open Access

Identification and validation of aging‑related genes in patients with multiple myeloma

  • Authors:
    • Huajing Liu
    • Senhua Song
    • Yingtao Wu
    • Yu Wang
    • Yueping Liu
    • Ying Liu
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China, Department of Hematology, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China, Hubei Key Laboratory of Central Nervous System Tumor and Intervention, Wuhan, Hubei 430000, P.R. China, Department of Disease Prevention and Control, General Hospital of Central Theater Command, Wuhan, Hubei 430000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 384
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    Published online on: July 2, 2026
       https://doi.org/10.3892/ol.2026.15739
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Abstract

This study aimed to identify and validate aging‑related genes (ARGs) implicated in multiple myeloma (MM), thereby advancing the understanding of the molecular mechanisms underlying the disease. mRNA expression data were retrieved from the Gene Expression Omnibus, and used as a training set to identify ARGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to explore the functional roles of the ARGs in MM. Candidate genes identified through least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM‑RFE) were compared using a Venn diagram, which revealed the overlap between the genes identified by the two algorithms. A receiver operating characteristic curve was generated based on the screening results. The candidate genes were further validated using the GSE39754 and GSE5900 datasets. Real‑time quantitative polymerase chain reaction (RT‑qPCR) was employed to validate the mRNA expression of key genes. Compared to normal individuals, patients with MM exhibited differential expression of 19 genes, of which 5 were upregulated and 14 downregulated. A total of 6 candidate genes (TXN, JUN, FOS, HIF1A, CAT and KCNA3) were identified through LASSO regression and SVM‑RFE screening. Among them, TXN exhibited the most significant differential expression, suggesting its potential as a diagnostic biomarker for MM. In addition, in vitro RT‑qPCR analysis confirmed that the mRNA levels of TXN in MM cells aligned with the bioinformatics findings, showing higher expression compared to normal B‑lymphocyte cell lines. In conclusion, this study identified age‑associated molecular patterns in MM and highlighted the diagnostic potential of TXN, offering novel insights for clinical applications in MM.
View Figures

Figure 1

ARGs in MM and normal samples. (A)
Volcano plot of the 454 DEGs in MM samples. Red dots indicate
significantly upregulated genes, while green dots indicate
significantly downregulated genes. (B) Heatmap of the 454 DEGs in
MM samples. Colors in the heat map indicate the fold changes of
differential expression (C) Venn diagram showing the identification
of ARGs in patients with MM. (D) Box plot of the 19 ARGs in MM and
normal samples. ***P<0.001. DEG, differentially expressed gene;
ARGs, aging-related DEGs; adj.P.Val, adjusted P-value; MM, multiple
myeloma; GEO, gene expression omnibus.

Figure 2

PPI analysis of the 19 ARGs. (A) PPIs
among the 18 ARGs. (B) Interaction count for each ARG. (C) Pearson
correlation analysis of the 18 ARGs. Numbers and related colors in
the figure indicate the Pearson correlation coefficient. PPI,
protein-protein interaction; ARGs, aging-related differentially
expressed genes.

Figure 3

Enrichment analysis of ARGs. (A) GO
enrichment analysis of 19 ARGs. (B) Kyoto encyclopedia of genes and
genomes enrichment analysis of 19 ARGs. (C) DO enrichment analysis
of 19 ARGs. ARGs, aging-related differentially expressed genes; GO,
gene ontology; DO, disease ontology.

Figure 4

Screening of candidate genes. (A)
LASSO logistic regression algorithm for candidate gene selection.
(B) SVM-RFE algorithm for candidate gene selection. (C) Venn
diagram showing the intersection of diagnostic markers identified
by the two algorithms. LASSO, least absolute shrinkage and
selection operator; SVM-RFE, support vector machine recursive
feature elimination; RMSE, root mean square error, a measure of the
differences between values predicted by a model and the actual
observed values.

Figure 5

ROC curves for the diagnostic
performance of the six candidate genes for multiple myeloma vs.
normal samples. (A) TXN; (B) JUN; (C) FOS; (D) HIF1A; (E) CAT; and
(F) KCNA3. AUC, area under the ROC curve; ROC, receiver operating
characteristic.

Figure 6

Validation of hub genes in other
datasets. (A-F) Expression levels of the candidate diagnostic
markers (A) TXN, (B) JUN, (C) FOS, (D) HIF1A, (E) CAT and (F) KCNA3
in the MM and normal samples in the validation cohort. (G-L) ROC
curve of the six candidate genes in MM and normal samples
(validation dataset). (G) TXN, (H) JUN, (I) FOS, (J) HIF1A, (K) CAT
and (L) KCNA3. AUC, area under the ROC curve; ROC, receiver
operating characteristic; MM, multiple myeloma.

Figure 7

Relative mRNA expression levels of TXN
analyzed in in normal and multiple myeloma cell lines. GM12878, a
normal, non-cancerous lymphoblastoid cell line, was set to 1 for
normalization and used as the reference for comparison with the
U266 and RPMI8226 cancer cell lines. Error bars represent the
standard deviation (or standard error of the mean) from at least
three independent experiments. **P<0.01 compared with
GM12878.
View References

1 

Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F and Anderson KC: Multiple myeloma. Nat Rev Dis Primers. 3:170462017. View Article : Google Scholar : PubMed/NCBI

2 

Palumbo A and Anderson K: Multiple myeloma. N Engl J Med. 364:1046–1060. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Rajkumar SV: Multiple myeloma: Every year a new standard? Hematol Oncol. 37 (Suppl 1):62–65. 2019. View Article : Google Scholar : PubMed/NCBI

4 

Raab MS, Podar K, Breitkreutz I, Richardson PG and Anderson KC: Multiple myeloma. Lancet. 374:324–339. 2009. View Article : Google Scholar : PubMed/NCBI

5 

De Winter G: Aging as disease. Med Health Care Philos. 18:237–243. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL and Bohr VA: Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol. 15:565–581. 2019. View Article : Google Scholar : PubMed/NCBI

7 

Fulop T, Larbi A, Douziech N, Levesque I, Varin A and Herbein G: Cytokine receptor signalling and aging. Mech Ageing Dev. 127:526–537. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Kanagal-Shamanna R, Beck DB and Calvo KR: Clonal hematopoiesis, inflammation, and hematologic malignancy. Annu Rev Pathol. 19:479–506. 2024. View Article : Google Scholar : PubMed/NCBI

9 

Urban VS, Cegledi A and Mikala G: Multiple myeloma, a quintessential malignant disease of aging: A geroscience perspective on pathogenesis and treatment. Geroscience. 45:727–746. 2023. View Article : Google Scholar : PubMed/NCBI

10 

Ullrich F, Bröckelmann PJ, Turki AT, Khan AM, Chiru ED, Vetter M, Tresckow BV, Wirth R, Cordoba R, Ortiz-Maldonado V, et al: Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma. J Immunother Cancer. 12:e0094622024. View Article : Google Scholar : PubMed/NCBI

11 

Visram A and Kourelis TV: Aging-associated immune system changes in multiple myeloma: The dark side of the moon. Cancer Treat Res Commun. 29:1004942021.PubMed/NCBI

12 

Zweegman S, Palumbo A, Bringhen S and Sonneveld P: Age and aging in blood disorders: Multiple myeloma. Haematologica. 99:1133–1137. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Yang B and Zhao S: Polydatin regulates proliferation, apoptosis and autophagy in multiple myeloma cells through mTOR/p70s6k pathway. Onco Targets Ther. 10:935–944. 2017. View Article : Google Scholar : PubMed/NCBI

14 

Yu L, Guo Q, Luo Z, Wang Y, Weng J, Chen Y, Liang W, Li Y, Zhang Y, Chen K, et al: TXN inhibitor impedes radioresistance of colorectal cancer cells with decreased ALDH1L2 expression via TXN/NF-κB signaling pathway. Br J Cancer. 127:637–648. 2022. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Fotiou D, Ntanasis-Stathopoulos I, Gavriatopoulou M and Dimopoulos MA: Multiple myeloma: Current and future management in the aging population. Maturitas. 138:8–13. 2020. View Article : Google Scholar : PubMed/NCBI

17 

Mafra A, Laversanne M, Marcos-Gragera R, Chaves HVS, Mcshane C, Bray F and Znaor A: The global multiple myeloma incidence and mortality burden in 2022 and predictions for 2045. J Natl Cancer Inst. 117:907–914. 2025. View Article : Google Scholar : PubMed/NCBI

18 

Casey M and Nakamura K: The cancer-immunity cycle in multiple myeloma. Immunotargets Ther. 10:247–260. 2021. View Article : Google Scholar : PubMed/NCBI

19 

Guo S, Tang Q, Gao X, Hu L, Hu K, Zhang H, Zhang Q, Lai Y, Liu Y, Wang Z, et al: EZH2 inhibition induces senescence via ERK1/2 signaling pathway in multiple myeloma. Acta Biochim Biophys Sin (Shanghai). 56:1055–1064. 2024. View Article : Google Scholar : PubMed/NCBI

20 

Wan Y, Wang J, Chen M, Wang J, Nan F, Huang H, Liu Z and Hou J: Dual roles of IRE1α inhibition in reversing mitochondrial ROS-induced CD8(+) T-cell senescence and exerting direct antitumor effects in multiple myeloma. J Immunother Cancer. 13:e0110442025. View Article : Google Scholar : PubMed/NCBI

21 

Alagpulinsa DA, Szalat RE, Poznansky MC and Shmookler Reis RJ: Genomic instability in multiple myeloma. Trends Cancer. 6:858–873. 2020. View Article : Google Scholar : PubMed/NCBI

22 

Plakhova N, Panagopoulos V, Cantley MD, Trainor LJ, Hewett DR, Clark KC, Gardiner J, Yong A, Lee C, Horvath N, et al: Age-related mesenchymal stromal cell senescence is associated with progression from MGUS to multiple myeloma. Leukemia. 39:1464–1475. 2025. View Article : Google Scholar : PubMed/NCBI

23 

Jiang ZX, Wang YN, Li ZY, Dai ZH, He Y, Chu K, Gu JY, Ji YX, Sun NX, Yang F and Li W: The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging. Cell Death Dis. 12:7442021. View Article : Google Scholar : PubMed/NCBI

24 

Abdul Sani NF, Amir Hamzah AIZ, Abu Bakar ZH, Mohd Yusof YA, Makpol S, Wan Ngah WZ and Damanhuri HA: Gene expression profile in different age groups and its association with cognitive function in healthy malay adults in Malaysia. Cells. 10:16112021. View Article : Google Scholar : PubMed/NCBI

25 

Liu X, Wang J, Shen K and Jin W: p53/HIF-1α regulates neuronal aging and autophagy in spinal cord ischemia/reperfusion injury. Mech Ageing Dev. 222:1120002024. View Article : Google Scholar : PubMed/NCBI

26 

Salazar G, Cullen A, Huang J, Zhao Y, Serino A, Hilenski L, Patrushev N, Forouzandeh F and Hwang HS: SQSTM1/p62 and PPARGC1A/PGC-1alpha at the interface of autophagy and vascular senescence. Autophagy. 16:1092–1110. 2020. View Article : Google Scholar : PubMed/NCBI

27 

Chen K, Qin C, Ji C, Yu Y, Wu Y, Xu L, Jiang Y and Zou G: Astragalus polysaccharide alleviates oxidative stress and senescence in chondrocytes in osteoarthritis via GCN2/ATF4/TXN axis. Int J Biol Macromol. 310((Pt 3)): 1432852025. View Article : Google Scholar : PubMed/NCBI

28 

Hernandez-Segura A, Nehme J and Demaria M: Hallmarks of Cellular Senescence. Trends Cell Biol. 2018.28. 436–453. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Matthews GM, de Matos Simoes R, Dhimolea E, Sheffer M, Gandolfi S, Dashevsky O, Sorrell JD and Mitsiades CS: NF-κB dysregulation in multiple myeloma. Semin Cancer Biol. 39:68–76. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu H, Song S, Wu Y, Wang Y, Liu Y and Liu Y: Identification and validation of aging‑related genes in patients with multiple myeloma. Oncol Lett 32: 384, 2026.
APA
Liu, H., Song, S., Wu, Y., Wang, Y., Liu, Y., & Liu, Y. (2026). Identification and validation of aging‑related genes in patients with multiple myeloma. Oncology Letters, 32, 384. https://doi.org/10.3892/ol.2026.15739
MLA
Liu, H., Song, S., Wu, Y., Wang, Y., Liu, Y., Liu, Y."Identification and validation of aging‑related genes in patients with multiple myeloma". Oncology Letters 32.3 (2026): 384.
Chicago
Liu, H., Song, S., Wu, Y., Wang, Y., Liu, Y., Liu, Y."Identification and validation of aging‑related genes in patients with multiple myeloma". Oncology Letters 32, no. 3 (2026): 384. https://doi.org/10.3892/ol.2026.15739
Copy and paste a formatted citation
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Spandidos Publications style
Liu H, Song S, Wu Y, Wang Y, Liu Y and Liu Y: Identification and validation of aging‑related genes in patients with multiple myeloma. Oncol Lett 32: 384, 2026.
APA
Liu, H., Song, S., Wu, Y., Wang, Y., Liu, Y., & Liu, Y. (2026). Identification and validation of aging‑related genes in patients with multiple myeloma. Oncology Letters, 32, 384. https://doi.org/10.3892/ol.2026.15739
MLA
Liu, H., Song, S., Wu, Y., Wang, Y., Liu, Y., Liu, Y."Identification and validation of aging‑related genes in patients with multiple myeloma". Oncology Letters 32.3 (2026): 384.
Chicago
Liu, H., Song, S., Wu, Y., Wang, Y., Liu, Y., Liu, Y."Identification and validation of aging‑related genes in patients with multiple myeloma". Oncology Letters 32, no. 3 (2026): 384. https://doi.org/10.3892/ol.2026.15739
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