Identification of the Key Genes Connected with Plasma Cells of Multiple Myeloma Using Expression Profiles

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2015 Aug 1

PMID 26229487

Citations 3

Authors

Kefeng Zhang

Zhongyang Xu

Zhaoyun Sun

Affiliations

Soon will be listed here.

Abstract

Objective: To uncover the potential regulatory mechanisms of the relevant genes that contribute to the prognosis and prevention of multiple myeloma (MM).

Methods: Microarray data (GSE13591) were downloaded, including five plasma cell samples from normal donors and 133 plasma cell samples from MM patients. Differentially expressed genes (DEGs) were identified by Student's t-test. Functional enrichment analysis was performed for DEGs using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Transcription factors and tumor-associated genes were also explored by mapping genes in the TRANSFAC, the tumor suppressor gene (TSGene), and tumor-associated gene (TAG) databases. A protein-protein interaction (PPI) network and PPI subnetworks were constructed by Cytoscape software using the Search Tool for the Retrieval of Interacting Genes (STRING) database.

Results: A total of 63 DEGs (42 downregulated, 21 upregulated) were identified. Functional enrichment analysis showed that HLA-DRB1 and VCAM1 might be involved in the positive regulation of immune system processes, and HLA-DRB1 might be related to the intestinal immune network for IgA production pathway. The genes CEBPD, JUND, and ATF3 were identified as transcription factors. The top ten nodal genes in the PPI network were revealed including HLA-DRB1, VCAM1, and TFRC. In addition, genes in the PPI subnetwork, such as HLA-DRB1 and VCAM1, were enriched in the cell adhesion molecules pathway, whereas CD4 and TFRC were both enriched in the hematopoietic cell pathway.

Conclusion: Several crucial genes correlated to MM were identified, including CD4, HLA-DRB1, TFRC, and VCAM1, which might exert their roles in MM progression via immune-mediated pathways. There might be certain regulatory correlations between HLA-DRB1, CD4, and TFRC.

Citing Articles

Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis.

Zhang Y, Wang C, Xia Q, Jiang W, Zhang H, Amiri-Ardekani E Front Med (Lausanne). 2023; 10:1001813.

PMID: 36860337 PMC: 9968813. DOI: 10.3389/fmed.2023.1001813.

Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis.

Lai X, Huang C, Nie X, Chen Q, Tang Y, Fu X Front Oncol. 2021; 11:720261.

PMID: 34631548 PMC: 8493032. DOI: 10.3389/fonc.2021.720261.

Identification of Candidate Genes and Therapeutic Agents for Light Chain Amyloidosis Based on Bioinformatics Approach.

Bai W, Wang H, Bai H Pharmgenomics Pers Med. 2020; 12:387-396.

PMID: 32099441 PMC: 6997413. DOI: 10.2147/PGPM.S228574.

References

Prabhala R, Neri P, Bae J, Tassone P, Shammas M, Allam C . Dysfunctional T regulatory cells in multiple myeloma. Blood. 2005; 107(1):301-4. PMC: 1895365. DOI: 10.1182/blood-2005-08-3101. View

Egan J, Shi C, Tembe W, Christoforides A, Kurdoglu A, Sinari S . Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides. Blood. 2012; 120(5):1060-6. PMC: 3412329. DOI: 10.1182/blood-2012-01-405977. View

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

Toes R, Ossendorp F, Offringa R, Melief C . CD4 T cells and their role in antitumor immune responses. J Exp Med. 1999; 189(5):753-6. PMC: 2192956. DOI: 10.1084/jem.189.5.753. View

Saito R, Smoot M, Ono K, Ruscheinski J, Wang P, Lotia S . A travel guide to Cytoscape plugins. Nat Methods. 2012; 9(11):1069-76. PMC: 3649846. DOI: 10.1038/nmeth.2212. View

Fonseca R, Barlogie B, Bataille R, Bastard C, Bergsagel P, Chesi M . Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res. 2004; 64(4):1546-58. DOI: 10.1158/0008-5472.can-03-2876. View

Sanz-Rodriguez F, Hidalgo A, Teixido J . Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Blood. 2001; 97(2):346-51. DOI: 10.1182/blood.v97.2.346. View

Boscacci R, Pfeiffer F, Gollmer K, Sevilla A, Martin A, Soriano S . Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing. Blood. 2010; 116(6):915-25. PMC: 3324225. DOI: 10.1182/blood-2009-11-254334. View

Storti P, DOnofrio G, Colla S, Airoldi I, Bolzoni M, Agnelli L . HOXB7 expression by myeloma cells regulates their pro-angiogenic properties in multiple myeloma patients. Leukemia. 2010; 25(3):527-37. DOI: 10.1038/leu.2010.270. View

10.

Eto D, Lao C, DiToro D, Barnett B, Escobar T, Kageyama R . IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation. PLoS One. 2011; 6(3):e17739. PMC: 3056724. DOI: 10.1371/journal.pone.0017739. View

11.

Traunecker A, Luke W, Karjalainen K . Soluble CD4 molecules neutralize human immunodeficiency virus type 1. Nature. 1988; 331(6151):84-6. DOI: 10.1038/331084a0. View

12.

Agnelli L, Forcato M, Ferrari F, Tuana G, Todoerti K, Walker B . The reconstruction of transcriptional networks reveals critical genes with implications for clinical outcome of multiple myeloma. Clin Cancer Res. 2011; 17(23):7402-12. DOI: 10.1158/1078-0432.CCR-11-0596. View

13.

van der Helm-van Mil A, Verpoort K, le Cessie S, Huizinga T, de Vries R, Toes R . The HLA-DRB1 shared epitope alleles differ in the interaction with smoking and predisposition to antibodies to cyclic citrullinated peptide. Arthritis Rheum. 2007; 56(2):425-32. DOI: 10.1002/art.22373. View

14.

Blotta S, Jakubikova J, Calimeri T, Roccaro A, Amodio N, Azab A . Canonical and noncanonical Hedgehog pathway in the pathogenesis of multiple myeloma. Blood. 2012; 120(25):5002-13. PMC: 3525024. DOI: 10.1182/blood-2011-07-368142. View

15.

Ruiz-Arguelles G, Katzmann J, Greipp P, Gonchoroff N, Garton J, Kyle R . Multiple myeloma: circulating lymphocytes that express plasma cell antigens. Blood. 1984; 64(2):352-6. View

16.

Wang M, Chen X, Zhang M, Zhu W, Cho K, Zhang H . Detecting significant single-nucleotide polymorphisms in a rheumatoid arthritis study using random forests. BMC Proc. 2009; 3 Suppl 7:S69. PMC: 2795970. DOI: 10.1186/1753-6561-3-s7-s69. View

17.

Chapman M, Lawrence M, Keats J, Cibulskis K, Sougnez C, Schinzel A . Initial genome sequencing and analysis of multiple myeloma. Nature. 2011; 471(7339):467-72. PMC: 3560292. DOI: 10.1038/nature09837. View

18.

Becker N . Epidemiology of multiple myeloma. Recent Results Cancer Res. 2011; 183():25-35. DOI: 10.1007/978-3-540-85772-3_2. View

19.

Gautier L, Cope L, Bolstad B, Irizarry R . affy--analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004; 20(3):307-15. DOI: 10.1093/bioinformatics/btg405. View

20.

Lionetti M, Biasiolo M, Agnelli L, Todoerti K, Mosca L, Fabris S . Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma. Blood. 2009; 114(25):e20-6. DOI: 10.1182/blood-2009-08-237495. View