Identification of Proteins Found to Be Significantly Altered when Comparing the Serum Proteome from Multiple Myeloma Patients with Varying Degrees of Bone Disease

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2014 Oct 18

PMID 25322877

Citations 20

Authors

Paul Dowling

Catriona Hayes

Kay Reen Ting

Abdul Hameed

Justine Meiller

Constantine Mitsiades

Kenneth C Anderson

Martin Clynes

Colin Clarke

Paul Richardson

Peter OGorman

Affiliations

Soon will be listed here.

Abstract

Background: Bone destruction is a feature of multiple myeloma, characterised by osteolytic bone destruction due to increased osteoclast activity and suppressed or absent osteoblast activity. Almost all multiple myeloma patients develop osteolytic bone lesions associated with severe and debilitating bone pain, pathologic fractures, hypercalcemia, and spinal cord compression, as well as increased mortality. Biomarkers of bone remodelling are used to identify disease characteristics that can help select the optimal management of patients. However, more accurate biomarkers are needed to effectively mirror the dynamics of bone disease activity.

Results: A label-free mass spectrometry-based strategy was employed for discovery phase analysis of fractionated patient serum samples associated with no or high bone disease. A number of proteins were identified which were statistically significantly correlated with bone disease, including enzymes, extracellular matrix glycoproteins, and components of the complement system.

Conclusions: Enzyme-linked immunosorbent assay of complement C4 and serum paraoxonase/arylesterase 1 indicated that these proteins were associated with high bone disease in a larger independent cohort of patient samples. These biomolecules may therefore be clinically useful in assessing the extent of bone disease.

Citing Articles

Bleeding and Thrombosis in Multiple Myeloma: Platelets as Key Players during Cell Interactions and Potential Use as Drug Delivery Systems.

Kulkarni A, Bazou D, Santos-Martinez M Int J Mol Sci. 2023; 24(21).

PMID: 37958838 PMC: 10647631. DOI: 10.3390/ijms242115855.

Using Proteomics Data to Identify Personalized Treatments in Multiple Myeloma: A Machine Learning Approach.

Katsenou A, OFarrell R, Dowling P, Heckman C, OGorman P, Bazou D Int J Mol Sci. 2023; 24(21).

PMID: 37958554 PMC: 10650823. DOI: 10.3390/ijms242115570.

Clinical Proteomics: Liquid Chromatography-Mass Spectrometry (LC-MS) Purification Systems.

Henry M, Meleady P Methods Mol Biol. 2023; 2699:255-269.

PMID: 37647003 DOI: 10.1007/978-1-0716-3362-5_14.

Proteomic Alteration in the Progression of Multiple Myeloma: A Comprehensive Review.

Ismail N, Mussa A, Al-Khreisat M, Yusoff S, Husin A, Johan M Diagnostics (Basel). 2023; 13(14).

PMID: 37510072 PMC: 10378430. DOI: 10.3390/diagnostics13142328.

An atlas of the bone marrow bone proteome in patients with dysproteinemias.

Ho M, Dasari S, Visram A, Drake M, Charlesworth M, Johnson K Blood Cancer J. 2023; 13(1):63.

PMID: 37105956 PMC: 10140150. DOI: 10.1038/s41408-023-00840-8.

References

Terpos E, Christoulas D, Kastritis E, Katodritou E, Papatheodorou A, Pouli A . The combination of lenalidomide and dexamethasone reduces bone resorption in responding patients with relapsed/refractory multiple myeloma but has no effect on bone formation: final results on 205 patients of the Greek myeloma study group. Am J Hematol. 2013; 89(1):34-40. DOI: 10.1002/ajh.23577. View

Khateeb J, Gantman A, Kreitenberg A, Aviram M, Fuhrman B . Paraoxonase 1 (PON1) expression in hepatocytes is upregulated by pomegranate polyphenols: a role for PPAR-gamma pathway. Atherosclerosis. 2009; 208(1):119-25. DOI: 10.1016/j.atherosclerosis.2009.08.051. View

Arioz D, Camuzcuoglu H, Toy H, Kurt S, Celik H, Erel O . Assessment of serum paraoxonase and arylesterase activity in patients with endometrial cancer. Eur J Gynaecol Oncol. 2010; 30(6):679-82. View

Vallet S, Pozzi S, Patel K, Vaghela N, Fulciniti M, Veiby P . A novel role for CCL3 (MIP-1α) in myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function. Leukemia. 2011; 25(7):1174-81. PMC: 4142423. DOI: 10.1038/leu.2011.43. View

Soe K, Delaisse J, Jakobsen E, Hansen C, Plesner T . Dosing related effects of zoledronic acid on bone markers and creatinine clearance in patients with multiple myeloma and metastatic breast cancer. Acta Oncol. 2013; 53(4):547-56. DOI: 10.3109/0284186X.2013.844358. View

Terpos E, Christoulas D, Kastritis E, Roussou M, Migkou M, Eleutherakis-Papaiakovou E . VTD consolidation, without bisphosphonates, reduces bone resorption and is associated with a very low incidence of skeletal-related events in myeloma patients post ASCT. Leukemia. 2013; 28(4):928-34. DOI: 10.1038/leu.2013.267. View

Roodman G . Pathogenesis of myeloma bone disease. Leukemia. 2008; 23(3):435-41. DOI: 10.1038/leu.2008.336. View

Dizdar O, Barista I, Kalyoncu U, Karadag O, Hascelik G, Cila A . Biochemical markers of bone turnover in diagnosis of myeloma bone disease. Am J Hematol. 2006; 82(3):185-91. DOI: 10.1002/ajh.20794. View

Jensen L, Kuhn M, Stark M, Chaffron S, Creevey C, Muller J . STRING 8--a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Res. 2008; 37(Database issue):D412-6. PMC: 2686466. DOI: 10.1093/nar/gkn760. View

10.

Zheng M, Zhang Z, Bemis K, Belch A, Pilarski L, Shively J . The systemic cytokine environment is permanently altered in multiple myeloma. PLoS One. 2013; 8(3):e58504. PMC: 3609759. DOI: 10.1371/journal.pone.0058504. View

11.

Sfiridaki A, Miyakis S, Pappa C, Tsirakis G, Alegakis A, Kotsis V . Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma. J Hematol Oncol. 2011; 4:22. PMC: 3102033. DOI: 10.1186/1756-8722-4-22. View

12.

Bentmann A, Kawelke N, Moss D, Zentgraf H, Bala Y, Berger I . Circulating fibronectin affects bone matrix, whereas osteoblast fibronectin modulates osteoblast function. J Bone Miner Res. 2009; 25(4):706-15. DOI: 10.1359/jbmr.091011. View

13.

Engstrom G, Hedblad B, Janzon L, Lindgarde F . Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study. Eur J Cardiovasc Prev Rehabil. 2007; 14(3):392-7. DOI: 10.1097/01.hjr.0000244582.30421.b2. View

14.

Terpos E, Dimopoulos M, Sezer O, Roodman D, Abildgaard N, Vescio R . The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group. Leukemia. 2010; 24(10):1700-12. DOI: 10.1038/leu.2010.173. View

15.

Bolzoni M, Storti P, Bonomini S, Todoerti K, Guasco D, Toscani D . Immunomodulatory drugs lenalidomide and pomalidomide inhibit multiple myeloma-induced osteoclast formation and the RANKL/OPG ratio in the myeloma microenvironment targeting the expression of adhesion molecules. Exp Hematol. 2012; 41(4):387-97.e1. DOI: 10.1016/j.exphem.2012.11.005. View

16.

Kyle R, Gertz M, Witzig T, Lust J, Lacy M, Dispenzieri A . Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003; 78(1):21-33. DOI: 10.4065/78.1.21. View

17.

Mackinnon E, El-Sohemy A, Rao A, Rao L . Paraoxonase 1 polymorphisms 172T→A and 584A→G modify the association between serum concentrations of the antioxidant lycopene and bone turnover markers and oxidative stress parameters in women 25-70 years of age. J Nutrigenet Nutrigenomics. 2010; 3(1):1-8. DOI: 10.1159/000316636. View

18.

Akcay M, Yilmaz I, Polat M, Akcay G . Serum paraoxonase levels in gastric cancer. Hepatogastroenterology. 2004; 50 Suppl 2:cclxxiii-cclxxv. View

19.

Tang C, Yang R, Huang T, Liu S, Fu W . Enhancement of fibronectin fibrillogenesis and bone formation by basic fibroblast growth factor via protein kinase C-dependent pathway in rat osteoblasts. Mol Pharmacol. 2004; 66(3):440-9. DOI: 10.1124/mol.66.3.. View

20.

Delorme S, Baur-Melnyk A . Imaging in multiple myeloma. Recent Results Cancer Res. 2011; 183:133-47. DOI: 10.1007/978-3-540-85772-3_7. View