A comparative analysis of transcriptomics of newly diagnosed multiple myeloma: exploring drug repurposing.

Angelos Giannakoulas, Marios Nikolaidis, Grigorios D Amoutzias, Nikolaos Giannakoulas
Author Information
  1. Angelos Giannakoulas: Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
  2. Marios Nikolaidis: Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Larissa, Greece.
  3. Grigorios D Amoutzias: Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Larissa, Greece.
  4. Nikolaos Giannakoulas: Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Abstract

Multiple myeloma (MM) is an incurable malignant plasma cell disorder characterized by the infiltration of clonal plasma cells in the bone marrow compartment. Gene Expression Profiling (GEP) has emerged as a powerful investigation tool in modern myeloma research enabling the dissection of the molecular background of MM and allowing the identification of gene products that could potentially serve as targets for therapeutic intervention. In this study we investigated shared transcriptomic abnormalities across newly diagnosed multiple myeloma (NDMM) patient cohorts. In total, publicly available transcriptomic data of 7 studies from CD138+ cells from 281 NDMM patients and 44 healthy individuals were integrated and analyzed. Overall, we identified 28 genes that were consistently differentially expressed (DE) between NDMM patients and healthy donors (HD) across various studies. Of those, 9 genes were over/under-expressed in more than 75% of NDMM patients. In addition, we identified 4 genes (MT1F, PURPL, LINC01239 and LINC01480) that were not previously considered to participate in MM pathogenesis. Meanwhile, by mining three drug databases (ChEMBL, IUPHAR/BPS and DrugBank) we identified 31 FDA-approved and 144 experimental drugs that target 8 of these 28 over/under-expressed MM genes. Taken together, our study offers new insights in MM pathogenesis and importantly, it reveals potential new treatment options that need to be further investigated in future studies.

Keywords

References

  1. Nat Rev Drug Discov. 2004 Aug;3(8):673-83 [PMID: 15286734]
  2. Cancer Metastasis Rev. 2008 Jun;27(2):253-61 [PMID: 18330678]
  3. Leukemia. 2012 Nov;26(11):2406-13 [PMID: 22722715]
  4. Blood. 2010 Oct 7;116(14):2543-53 [PMID: 20574050]
  5. Cells. 2021 Aug 02;10(8): [PMID: 34440730]
  6. Leukemia. 2010 Mar;24(3):629-37 [PMID: 20054351]
  7. Blood. 2014 Sep 11;124(11):1765-76 [PMID: 25061176]
  8. Nat Med. 2023 Apr;29(4):869-879 [PMID: 37069359]
  9. Exp Cell Res. 2015 Mar 1;332(1):24-38 [PMID: 25637218]
  10. N Engl J Med. 2003 Dec 25;349(26):2483-94 [PMID: 14695408]
  11. Am J Cancer Res. 2022 Jul 15;12(7):2950-2965 [PMID: 35968339]
  12. N Engl J Med. 2006 Mar 30;354(13):1362-9 [PMID: 16571879]
  13. Biochem Biophys Res Commun. 1993 Apr 30;192(2):553-60 [PMID: 8387282]
  14. J Biol Chem. 2014 May 16;289(20):14132-44 [PMID: 24706764]
  15. Cell Death Dis. 2021 Nov 10;12(11):1070 [PMID: 34759263]
  16. Br J Haematol. 2017 Sep;178(5):781-793 [PMID: 28597546]
  17. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Apr;17(2):382-4 [PMID: 19379571]
  18. Haematologica. 2008 Mar;93(3):431-8 [PMID: 18268286]
  19. Ecancermedicalscience. 2014 Jul 10;8:442 [PMID: 25075216]
  20. Genome Biol. 2014;15(12):550 [PMID: 25516281]
  21. Biochem Biophys Res Commun. 2020 Jul 30;528(3):586-593 [PMID: 32505357]
  22. Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):E3-12 [PMID: 22135465]
  23. BMC Cancer. 2023 Apr 6;23(1):317 [PMID: 37024813]
  24. Bioinformatics. 2014 Aug 1;30(15):2114-20 [PMID: 24695404]
  25. Cancer Res. 2005 Mar 1;65(5):1700-9 [PMID: 15753365]
  26. Leukemia. 2011 Jul;25(7):1174-81 [PMID: 21403648]
  27. Cancer Res. 2007 Apr 1;67(7):2982-9 [PMID: 17409404]
  28. Immunol Res. 2014 May;58(2-3):179-85 [PMID: 24522698]
  29. Haematologica. 2019 Feb;104(2):e72-e76 [PMID: 30213829]
  30. Nat Rev Cancer. 2013 Sep;13(9):637-51 [PMID: 23884378]
  31. Leukemia. 2013 Aug;27(8):1729-37 [PMID: 23478664]
  32. Immunol Res. 2005;31(2):119-31 [PMID: 15778510]
  33. Am J Hematol. 2022 Aug;97(8):1086-1107 [PMID: 35560063]
  34. Peptides. 2020 Sep;131:170347 [PMID: 32569606]
  35. Cytometry B Clin Cytom. 2016 Jan;90(1):61-72 [PMID: 26100534]
  36. Br J Haematol. 2002 Oct;119(1):70-8 [PMID: 12358905]
  37. N Engl J Med. 2018 Jan 18;378(3):241-249 [PMID: 29342381]
  38. Biochim Biophys Acta. 2012 Jun;1822(6):918-26 [PMID: 22426038]
  39. Nucleic Acids Res. 2023 Jan 6;51(D1):D1003-D1009 [PMID: 36243972]
  40. Bioengineered. 2022 Jan;13(1):1359-1376 [PMID: 35012438]
  41. Blood. 2006 Sep 15;108(6):2020-8 [PMID: 16728703]
  42. Clin Cancer Res. 2010 Feb 15;16(4):1094-9 [PMID: 20145169]
  43. Oncologist. 2020 Sep;25(9):e1406-e1413 [PMID: 32335971]
  44. Int J Cancer. 2007;120 Suppl 12:40-61 [PMID: 17405120]
  45. Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5 [PMID: 23193258]
  46. Nat Med. 2018 Dec;24(12):1867-1876 [PMID: 30523328]
  47. Genome Biol. 2010;11(3):R25 [PMID: 20196867]
  48. Br J Pharmacol. 2018 Jan;175(1):3-17 [PMID: 29059473]
  49. Nat Commun. 2021 Sep 14;12(1):5450 [PMID: 34521827]
  50. Blood. 1998 Feb 1;91(3):806-12 [PMID: 9446640]
  51. Leukemia. 2007 Mar;21(3):541-9 [PMID: 17252022]
  52. Leukemia. 2003 Apr;17(4):764-74 [PMID: 12682635]
  53. Cancers (Basel). 2021 Apr 09;13(8): [PMID: 33918655]
  54. Drug Discov Today. 2019 Oct;24(10):2076-2085 [PMID: 31238113]
  55. Bioinformatics. 2010 Jan 1;26(1):139-40 [PMID: 19910308]
  56. Leukemia. 2005 Aug;19(8):1466-70 [PMID: 15959533]
  57. Mol Cell Biol. 1995 May;15(5):2600-11 [PMID: 7739541]
  58. Curr Opin Virol. 2017 Feb;22:77-88 [PMID: 28086150]
  59. FEBS Lett. 2020 Feb;594(3):452-465 [PMID: 31561267]
  60. Blood. 2007 Mar 15;109(6):2276-84 [PMID: 17105813]
  61. Blood. 2013 Jul 11;122(2):219-26 [PMID: 23699600]
  62. Blood. 2016 May 12;127(19):2355-6 [PMID: 27020089]
  63. Int J Hematol Oncol. 2022 Apr 26;11(2):IJH39 [PMID: 35663420]
  64. Ann Oncol. 2021 Mar;32(3):309-322 [PMID: 33549387]
  65. Sci Rep. 2020 Nov 25;10(1):20508 [PMID: 33239656]
  66. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  67. Bone. 2008 Apr;42(4):669-80 [PMID: 18294945]
  68. J Hematol Oncol. 2018 Aug 23;11(1):107 [PMID: 30139373]
  69. Headache. 2018 Nov;58 Suppl 3:238-275 [PMID: 30242830]
  70. Cell Rep. 2017 Sep 5;20(10):2408-2423 [PMID: 28877474]
  71. Regul Pept. 2003 Apr 15;112(1-3):175-83 [PMID: 12667640]
  72. Int J Biochem Cell Biol. 2008;40(8):1443-51 [PMID: 18325824]
  73. J Cancer Res Clin Oncol. 2016 Oct;142(10):2141-58 [PMID: 27530445]
  74. Eur Heart J. 2022 Oct 11;43(38):3618-3731 [PMID: 36017548]
  75. Blood. 2008 Jul 1;112(1):196-207 [PMID: 18305214]
  76. Haematologica. 2014 Aug;99(8):1365-72 [PMID: 24816239]
  77. Gynecol Oncol. 2017 Dec;147(3):654-662 [PMID: 29050779]
  78. Adv Sci (Weinh). 2022 Jun;9(18):e2200818 [PMID: 35570408]
  79. Br J Haematol. 2019 Mar;184(6):1052-1055 [PMID: 29726006]
  80. Pathol Oncol Res. 2023 Mar 22;29:1611083 [PMID: 37033323]
  81. Clin Cancer Res. 2010 Mar 15;16(6):1856-64 [PMID: 20215539]
  82. Yale J Biol Med. 2003;76(2):55-62 [PMID: 15369632]
  83. Blood. 2001 Jun 1;97(11):3349-53 [PMID: 11369623]
  84. Mol Med Rep. 2019 Jun;19(6):4998-5006 [PMID: 31059022]
  85. Mol Cell Biol. 2022 Dec 15;42(12):e0028922 [PMID: 36342127]
  86. J Clin Invest. 2007 Oct;117(10):3107-17 [PMID: 17823654]
  87. Leukemia. 2009 Dec;23(12):2210-21 [PMID: 19798094]
  88. Blood. 2021 Oct 28;138(17):1583-1589 [PMID: 34133718]
  89. Leukemia. 2009 Oct;23(10):1904-12 [PMID: 19554029]
  90. Leuk Lymphoma. 2005 Dec;46(12):1699-707 [PMID: 16263571]
  91. J Clin Oncol. 2008 Oct 10;26(29):4798-805 [PMID: 18591550]

Word Cloud

Created with Highcharts 10.0.0MMNDMMmyelomagenesmultiplestudiespatientsidentifieddrugplasmacellsgenestudyinvestigatedtranscriptomicacrossnewlydiagnosedhealthy28over/under-expressedPURPLpathogenesisnewtranscriptomicsrepurposingMultipleincurablemalignantcelldisordercharacterizedinfiltrationclonalbonemarrowcompartmentGeneExpressionProfilingGEPemergedpowerfulinvestigationtoolmodernresearchenablingdissectionmolecularbackgroundallowingidentificationproductspotentiallyservetargetstherapeuticinterventionsharedabnormalitiespatientcohortstotalpubliclyavailabledata7CD138+28144individualsintegratedanalyzedOverallconsistentlydifferentiallyexpressedDEdonorsHDvarious975%addition4MT1FLINC01239LINC01480previouslyconsideredparticipateMeanwhileminingthreedatabasesChEMBLIUPHAR/BPSDrugBank31FDA-approved144experimentaldrugstarget8Takentogetheroffersinsightsimportantlyrevealspotentialtreatmentoptionsneedfuturecomparativeanalysismyeloma:exploringADMadrenomedullinexpressionprofiling

Similar Articles

Cited By