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Evaluation of Genes and Molecular Pathways Involved in the Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma: A Systems Biology Approach

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Abstract

Today, Monoclonal Gammopathy of Undetermined Significance (MGUS) is known as a plasma cell malignancy susceptible to evolving into the life-threatening stage, multiple myeloma (MM), without prominent clinical manifestations. Despite the discovery of advanced therapies and multiple pathogenic markers, the complexity of MM development has made it an incurable malignancy. In this study, the microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the LIMMA package of R-software to determine differentially expressed genes (DEGs) in MGUS and MM compared to the control samples. Enrichment analysis of DEGs was evaluated using the GeneCodis4 software. Protein–protein interaction (PPI) networks were constructed via the GeneMANIA database, and Cytoscape visualized them. The Molecular Complex Detection (MCODE) plugin from Cytoscape was used to identify the key modules from the PPI network. Afterward, the hub genes were recognized using the cytoHubba plug-in in Cytoscape. Eventually, the correlation between hub-DEGs and MM-specific survival was evaluated via the PrognoScan database. A total of 138 (MM-normal) and 136 (MGUS-normal) DEGs were obtained from the datasets, and 62 common DEGs between MGUS and MM diseases (26 up-regulated and 36 down-regulated genes) were screened out for subsequent analyses. Following enrichment analyses and the PPI network's evaluation, FOS, FOSB, JUN, MAFF, and PPP1R15A involved in the progression of MGUS to MM were detected as the hub genes. The survival analysis revealed that FOS, FOSB, and JUN among hub genes were significantly associated with disease-specific survival (DSS) in MM. Identifying the genes involved in the progression of MGUS to MM can help in the design of preventive strategies as well as the treatment of patients. In addition, their evaluation can be effective in the survival of patients.

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Data Availability

This is a review study, and it is not an original. Data availability is corresponding author responsibility.

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Acknowledgements

The authors appreciate and thank the efforts of the Center for the Development of Clinical Researches of the Educational and Therapeutic Research Complex of Hazrat-e Rasool General Hospital.

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Authors and Affiliations

  1. Department of Internal Medicine, Lorestan University of Medical Science, Khorramabad, Iran

    Parisa Khalili

  2. Department of Bioprocess Engineering, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran

    Reza Maddah

  3. Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mohsen Maleknia

  4. Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Mohsen Maleknia

  5. Department of Internal Medicine, School of Medicine Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran

    Bahareh Shateri Amiri

  6. School of Medicine, Yasuj University of Medical Science, Yasuj, Iran

    Fatemeh Forouzani

  7. Department of Surgery, Lorestan University of Medical Science, Khorramabad, Iran

    Afshin Hasanvand

  8. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Iranian Blood Transfusion Organization (IBTO), Tehran, Iran

    Hadi Rezaeeyan

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HR conceived the manuscript and revised it. MM and BSA wrote the manuscript. RM and AH analysis of data. PK conducted the revise. FF conducted the native English.

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Correspondence to Hadi Rezaeeyan.

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This article does not contain any studies with human participants or animals performed by any of the authors. All the procedures performed in the studies involving human participants were in accordance with ethical standards of Local Ethics Committee of Iran University of Medical Sciences (IR.IUMS.REC.1401.607), as well as 1964 Helsinki Declaration.

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Khalili, P., Maddah, R., Maleknia, M. et al. Evaluation of Genes and Molecular Pathways Involved in the Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma: A Systems Biology Approach. Mol Biotechnol 65, 1275–1286 (2023). https://doi.org/10.1007/s12033-022-00634-6

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