Iranian Journal of Medical Sciences

Iranian Journal of Medical Sciences

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Journal Team

Publication Ethics

Indexing and Abstracting

Related Links

Peer Review Process

Journal Metrics

Exploring Differentially Expressed Genes and Immune Modulation in Diffuse Large B-Cell Lymphoma through RNA Sequencing Analysis

Document Type : Original Article(s)

Authors

1 UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia

2 Codon Genomics Sdn Bhd, Seri Kembangan Selangor Darul Ehsan, Malaysia

3 Cell Therapy Center, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia

10.30476/ijms.2023.100149.3234

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is globally recognized as the most prevalent and aggressive subtype of non-Hodgkin lymphoma. While conventional treatments are effective initially, the disease can become resistant or relapse over time. The study aimed to examine the differentially expressed genes at the transcriptome level and molecular pathways in DLBCL patients. 
Methods: This investigation utilized RNA sequencing analysis to compare differentially expressed gene samples from five diffuse large B-cell lymphoma patients with two healthy volunteers. These participants were admitted to UKM Medical Center, Kuala Lumpur between 2019 and 2020. The differentially expressed genes were conducted using the DESeq2 R package (version 1.10.1) using a negative binomial distribution model. The obtained P values were corrected with the Benjamin and Hochberg method and identified using a False Discovery Rate threshold of <0.05, with log2 fold change (FC) of ≥2 or ≤-2. 
Results: Results showed 73 differentially expressed genes between the two groups, among which 70 genes were downregulated, and three genes were upregulated. The differentially expressed genes analyzed with the Reactome pathway were significantly associated with the downregulation of antimicrobial humoral response (P<0.001), neutrophil degranulation (P<0.001), chemokine receptors bind chemokines (P=0.028), defensins (P=0.028) and metabolism of angiotensinogen (P=0.040). 
Conclusion: These findings suggest that the identified pathways may contribute to cancer progression and weaken the immune response in diffuse large B-cell lymphoma patients. This study offers fresh insights into previously undiscovered downstream targets and pathways modulated by diffuse large B-cell lymphoma.

Keywords

References
  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-49. doi: 10.3322/caac.21660. PubMed PMID: 33538338.
  2. Satou A, Bennani NN, Feldman AL. Update on the classification of T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol. 2019;12:833-43. doi: 10.1080/17474086.2019.1647777. PubMed PMID: 31365276; PubMed Central PMCID: PMCPMC6763378.
  3. Poletto S, Novo M, Paruzzo L, Frascione PMM, Vitolo U. Treatment strategies for patients with diffuse large B-cell lymphoma. Cancer Treat Rev. 2022;110:102443. doi: 10.1016/j.ctrv.2022.102443. PubMed PMID: 35933930.
  4. Sawalha Y. Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Look at the Approved and Emerging Therapies. J Pers Med. 2021;11. doi: 10.3390/jpm11121345. PubMed PMID: 34945817; PubMed Central PMCID: PMCPMC8708171.
  5. Hong M, Tao S, Zhang L, Diao LT, Huang X, Huang S, et al. RNA sequencing: new technologies and applications in cancer research. J Hematol Oncol. 2020;13:166. doi: 10.1186/s13045-020-01005-x. PubMed PMID: 33276803; PubMed Central PMCID: PMCPMC7716291.
  6. Peymani F, Farzeen A, Prokisch H. RNA sequencing role and application in clinical diagnostic. Pediatr Investig. 2022;6:29-35. doi: 10.1002/ped4.12314. PubMed PMID: 35382420; PubMed Central PMCID: PMCPMC8960934.
  7. Serrano Lopez J, Jimenez-Jimenez C, Chutipongtanate S, Serrano J, Rodriguez-Moreno M, Jimenez A, et al. High-throughput RNA sequencing transcriptome analysis of ABC-DLBCL reveals several tumor evasion strategies. Leuk Lymphoma. 2022;63:1861-70. doi: 10.1080/10428194.2022.2056173. PubMed PMID: 35379068.
  8. Sheng L, Fu D, Cao Y, Huo Y, Wang S, Shen R, et al. Integrated Genomic and Transcriptomic Analyses of Diffuse Large B-Cell Lymphoma With Multiple Abnormal Immunologic Markers. Front Oncol. 2022;12:790720. doi: 10.3389/fonc.2022.790720. PubMed PMID: 35237512; PubMed Central PMCID: PMCPMC8882913.
  9. Zhou M, Zhao H, Xu W, Bao S, Cheng L, Sun J. Discovery and validation of immune-associated long non-coding RNA biomarkers associated with clinically molecular subtype and prognosis in diffuse large B cell lymphoma. Mol Cancer. 2017;16:16. doi: 10.1186/s12943-017-0580-4. PubMed PMID: 28103885; PubMed Central PMCID: PMCPMC5248456.
  10. Xu D, Lu W. Defensins: A Double-Edged Sword in Host Immunity. Front Immunol. 2020;11:764. doi: 10.3389/fimmu.2020.00764. PubMed PMID: 32457744; PubMed Central PMCID: PMCPMC7224315.
  11. Xiong S, Dong L, Cheng L. Neutrophils in cancer carcinogenesis and metastasis. J Hematol Oncol. 2021;14:173. doi: 10.1186/s13045-021-01187-y. PubMed PMID: 34674757; PubMed Central PMCID: PMCPMC8529570.
  12. Li WY, Li QW, Han ZS, Jiang ZL, Yang H, Li J, et al. Growth suppression effects of recombinant adenovirus expressing human lactoferrin on cervical cancer in vitro and in vivo. Cancer Biother Radiopharm. 2011;26:477-83. doi: 10.1089/cbr.2010.0937. PubMed PMID: 21834714.
  13. Kutok JL, Yang X, Folkerth R, Adra CN. Characterization of the expression of HTm4 (MS4A3), a cell cycle regulator, in human peripheral blood cells and normal and malignant tissues. J Cell Mol Med. 2011;15:86-93. doi: 10.1111/j.1582-4934.2009.00925.x. PubMed PMID: 19818099; PubMed Central PMCID: PMCPMC3822496.
  14. Zhang L, Soares MP, Guan Y, Matheravidathu S, Wnek R, Johnson KE, et al. Functional expression and characterization of macaque C-C chemokine receptor 3 (CCR3) and generation of potent antagonistic anti-macaque CCR3 monoclonal antibodies. J Biol Chem. 2002;277:33799-810. doi: 10.1074/jbc.M205488200. PubMed PMID: 12101185.
  15. Stellato C, Brummet ME, Plitt JR, Shahabuddin S, Baroody FM, Liu MC, et al. Expression of the C-C chemokine receptor CCR3 in human airway epithelial cells. J Immunol. 2001;166:1457-61. doi: 10.4049/jimmunol.166.3.1457. PubMed PMID: 11160184.
  16. Yuan J, Liu Y, Yu J, Dai M, Zhu Y, Bao Y, et al. Gene knockdown of CCR3 reduces eosinophilic inflammation and the Th2 immune response by inhibiting the PI3K/AKT pathway in allergic rhinitis mice. Sci Rep. 2022;12:5411. doi: 10.1038/s41598-022-09467-4. PubMed PMID: 35354939; PubMed Central PMCID: PMCPMC8969185.
  17. Capucetti A, Albano F, Bonecchi R. Multiple Roles for Chemokines in Neutrophil Biology. Front Immunol. 2020;11:1259. doi: 10.3389/fimmu.2020.01259. PubMed PMID: 32733442; PubMed Central PMCID: PMCPMC7363767.
  18. Park SH, Das BB, Casagrande F, Tian Y, Nothnagel HJ, Chu M, et al. Structure of the chemokine receptor CXCR1 in phospholipid bilayers. Nature. 2012;491:779-83. doi: 10.1038/nature11580. PubMed PMID: 23086146; PubMed Central PMCID: PMCPMC3700570.
  19. Lomakina EB, Waugh RE. Signaling and Dynamics of Activation of LFA-1 and Mac-1 by Immobilized IL-8. Cell Mol Bioeng. 2010;3:106-16. doi: 10.1007/s12195-009-0099-x. PubMed PMID: 21532911; PubMed Central PMCID: PMCPMC3084010.
Iranian Journal of Medical Sciences

Articles InPress, Corrected Proof
Available Online from 09 March 2024
Files
History
  • Received: 17 September 2023
  • Revised: 29 October 2023
  • Accepted: 19 November 2023
Share
How to cite
Statistics