Transcriptomic Insights into Gene and miRNA Dynamics Shaping EMT in Multiple Myeloma

3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 315-318) 

 

АУТОР(И) / AUTHOR(S): Halime Sena Ekmekci, Oguzhan Akgun, Aysen Sagnak, Elif Erturk, Fazıl Cagri Hunutlu, Tuba Ersal, Fahir Ozkalemkas, Vildan Ozkocaman, Hulya Ozturk Nazlioglu, Ferda Ari

 

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DOI:  10.46793/ICCBIKG25.315E

САЖЕТАК / ABSTRACT:

Multiple myeloma (MM) is characterized by the proliferation of plasma cells (PCs) within the bone marrow microenvironment. While usually confined to the bone marrow, MM can spread through subclones that form plasmacytomas. Extramedullary disease (EMD) represents an aggressive form of MM, in which a clone or subclone grows independently of the bone marrow microenvironment. Epithelial–mesenchymal transition (EMT) is a process in which epithelial cells lose adhesion properties and acquire invasive, mesenchymal traits. A limited number of studies suggest that EMT-like features in MM may contribute to the development of EMD; however, the role of EMT in MM remains unclear. In this study, potential EMT-related biomarkers in MM were investigated using bioinformatic approaches. A total of 963 EMT-related genes were identified by screening five databases, and 689 corresponding miRNAs were determined using the mirNet package in R. The association of the identified genes and miRNAs with MM was evaluated using expression data from 45 MM patient samples in the GSE125364 dataset from the NCBI GEO database. Differentially expressed genes and miRNAs were ranked using the degree scoring method, and the top 20 genes and 20 miRNAs significantly associated with MM were identified. These findings may provide valuable insights into the role of the EMT process in MM.

КЉУЧНЕ РЕЧИ / KEYWORDS:

multiple myeloma, EMD, EMT, bioinformatics

ПРОЈЕКАТ / ACKNOWLEDGEMENT:

This research is supported by the Bursa Uludağ University Research Fund under project number TGA-2024-1921. We thank Bursa Uludag Molecular Cancer Research Laboratory (BUMKAL) for their valuable support and contributions to this study.

ЛИТЕРАТУРА / REFERENCES:

  • M. Hussain, S. Yellapragada, S. Al Hadidi., Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article, Blood and Lymphatic Cancer: Targets and Therapy, 13 (2023) 33–57.
  • L. Rosiñol, M. Beksac, E. Zamagni, N.W.C.J. Van de Donk, K.C. Anderson, A. Badros, J. Caers, Cavo, M.A. Dimopoulos, A. Dispenzieri, H. Einsele, M. Engelhardt, C. Fernández de Larrea, Gahrton, F. Gay, R. Hájek, V. Hungria, A. Jurczyszyn, N. Kröger, R.A. Kyle, J. Bladé., Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations, British Journal of Haematology, 194 (2021) 496–507.
  • J. Bladé, M. Beksac, J. Caers, A. Jurczyszyn, M. von Lilienfeld-Toal, P. Moreau, L. Rasche, L. Rosiñol, S.Z. Usmani, E. Zamagni, P. Richardson., Extramedullary disease in multiple myeloma: a systematic literature review, Blood Cancer Journal, 12 (2022) 45.
  • A. M. Roccaro, Y. Mishima, A. Sacco, M. Moschetta, Y.T. Tai, J. Shi, Y. Zhang, M.R. Reagan, D. Huynh, Y. Kawano, I. Sahin, M. Chiarini, S. Manier, M. Cea, Y. Aljawai, S. Glavey, E. Morgan, C. Pan, F. Michor, P. Cardarelli, I.M. Ghobrial., CXCR4 Regulates Extra-Medullary Myeloma through Epithelial-Mesenchymal-Transition-like Transcriptional Activation, Cell Reports, 12 (2015) 622–635.
  • M. Weinstock, I.M. Ghobrial., Extramedullary multiple myeloma, Leukemia & Lymphoma, 54 (2013) 1135–1141.
  • E. Pretzsch, F. Bösch, J. Neumann, P. Ganschow, A. Bazhin, M. Guba, J. Werner, M. Angele., Mechanisms of Metastasis in Colorectal Cancer and Metastatic Organotropism: Hematogenous versus Peritoneal Spread, Journal of Oncology, 2019 (2019) 7407190.
  • M. Hirao, K. Yamazaki, K. Watanabe, K. Mukai, S. Hirose, M. Osada, Y. Tsukada, H. Kunieda, Denda, T. Kikuchi, H. Sugimori, S. Okamoto, Y. Hattori., Negative E-cadherin expression on bone marrow myeloma cell membranes is associated with extramedullary disease, F1000Research, 11 (2022) 245.
  • M. Kanehisa, M. Furumichi, T. Mao, Y. Sato, K. Morishima., KEGG: new perspectives on genomes, pathways, diseases and drugs, Nucleic Acids Research, (2017) D353–D361.
  • J. Villaveces, R. Jimenez, B. Habermann., KEGG: Kyoto Encyclopedia of Genes and Genomes, F1000Research, 3 (2014).
  • S. Carbon, E. Douglass, N. Dunn, B. Good, N.L. Harris, S.E. Lewis, M. Westerfield., The Gene Ontology Resource: 20 years and still GOing strong, Nucleic Acids Research, 47 (2019) D330– D338.
  • M. Ashburner, C.B. A, J.B. A, D. B, H. B, M.C.J., G. S., Gene Ontology: tool for the unification of biology, Nature Genetics, 25 (2000) 25–29.
  • G. Joshi-Tope, I. Vastrik, G.R. Gopinath, L. Matthews, E. Schmidt, M. Gillespie, L. Stein., The genome knowledgebase: A resource for biologists and bioinformaticists, Cold Spring Harbor Symposia on Quantitative Biology, 68 (2003) 237–243.
  • L. D. Stein., Using the Reactome Database, Current Protocols in Bioinformatics, 7 (2004).
  • M. Zhao, Y. Liu, C. Zheng, H. Qu., dbEMT 2.0: An updated database for epithelial- mesenchymal transition genes with experimentally verified information and precalculated regulation information for cancer metastasis, Journal of Genetics and Genomics, 46 (2019) 595– 597.
  • S. V. Vasaikar, A.P. Deshmukh, P. den Hollander, S. Addanki, N.A. Kuburich, S. Kudaravalli, S.A. Mani., EMTome: a resource for pan-cancer analysis of epithelial-mesenchymal transition genes and signatures, British Journal of Cancer, 124 (2021) 259–269.
  • L. Chang, G. Zhou, O. Soufan, J. Xia., miRNet 2.0: Network-based visual analytics for miRNA functional analysis and systems biology, Nucleic Acids Research, 48 (2020) W244–W251.
  • M. I. Love, W. Huber, S. Anders., Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biology, 15 (2014) 550.
  • N. Wani, D. Barh, K. Raza., Modular Network Inference Between Mirna-Mrna Expression Profiles Using Weighted Co-Expression Network Analysis, Journal of Integrative Bioinformatics, 18 (2021) 20210029.