Immune marker changes and risk of multiple myeloma : a nested case-control study using repeated prediagnostic blood samples

Biomarkers reliably predicting progression to multiple myeloma (MM) are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1 alpha), vascular endothelial growth factor (VEGF), fibroblast growth facto...

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Bibliographic Details
Published in:Haematologica
Main Authors: Späth, Florentin, Wibom, Carl, Krop, Esmeralda, Izarra Santamaria, Antonio, Johansson, Ann Sofie, Bergdahl, Ingvar, Hultdin, Johan, Vermeulen, Roel, Melin, Beatrice S.
Format: Article in Journal/Newspaper
Language:English
Published: Umeå universitet, Onkologi 2019
Subjects:
prospective longitudinal study
multiple myeloma risk
progression
marker trajectories
Clinical Medicine
Klinisk medicin
Northern Sweden
Online Access:http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-156420
https://doi.org/10.3324/haematol.2019.216895
Description
Summary:Biomarkers reliably predicting progression to multiple myeloma (MM) are lacking. Myeloma risk has been associated with low blood levels of monocyte chemotactic protein-3 (MCP-3), macrophage inflammatory protein-1 alpha (MIP-1 alpha), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), fractalkine, and transforming growth factor-alpha (TGF-alpha). In this study, we aimed to replicate these findings and study the individual dynamics of each marker in a prospective longitudinal cohort, thereby examining their potential as markers of myeloma progression. For this purpose, we identified 65 myeloma cases and 65 matched cancer-free controls each with two donated blood samples within the Northern Sweden Health and Disease Study. The first and repeated samples from myeloma cases were donated at a median 13 and 4 years, respectively, before the myeloma was diagnosed. Known risk factors for progression were determined by protein-, and immunofixation electrophoresis, and free light chain assays. We observed lower levels of MCP-3, VEGF, FGF-2, and TGF-alpha in myeloma patients than in controls, consistent with previous data. We also observed that these markers decreased among future myeloma patients while remaining stable in controls. Decreasing trajectories were noted for TGF-alpha (P=2.5 x 10(-4)) indicating progression to MM. Investigating this, we found that low levels of TGF-alpha assessed at the time of the repeated sample were independently associated with risk of progression in a multivariable model (hazard ratio = 3.5; P=0.003). TGF-alpha can potentially improve early detection of MM. Originally included in thesis in manuscript form

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