Increased plasma endostatin and GDF15 in indolent non-Hodgkin lymphoma

  • Josefin Hidman Department of Medical Science, Uppsala University, Uppsala, Sweden; Centre for Clinical Research Västmanland, Västmanland County Hospital, Uppsala University, Uppsala, Sweden; and Department of Medicine, Västmanland County Hospital, Västerås, Sweden
  • Anders Larsson Department of Medical Science, Uppsala University, Uppsala, Sweden; and Department of Clinical Chemistry, Uppsala University Hospital, Uppsala, Sweden
  • Måns Thulin Department of Mathematics, Uppsala University, Uppsala, Sweden
  • Torbjörn Karlsson Department of Medical Science, Uppsala University, Uppsala, Sweden; and Department of Haematology, Uppsala University Hospital, Uppsala, Sweden
Keywords: Growth differentiation factor 15, endostatin, matrix metalloproteinase 9, neutrophil gelatin-aseassociated lipocalin, non-Hodgkin lymphoma, angiogenesis


Background: Increased microvascular density correlates with more advanced disease and unfavorable overall survival in non-Hodgkin lymphoma (NHL), suggesting that angiogenesis is important for disease progression. However, studies of anti-angiogenic agents in NHL patients, have generally not shown favorable outcomes. The aim of this study was to investigate whether plasma levels of a subset of angiogenesis-associated proteins are increased in indolent B-cell derived NHL (B-NHL) and to investigate whether the levels differ between patients with asymptomatic versus symptomatic disease.

Methods: Plasma levels of growth differentiation factor 15 (GDF15), endostatin, matrix metalloproteinase 9 (MMP9), neutrophil gelatinase-associated lipocalin (NGAL), long pentraxin 3 (PTX3), and galectin 3 (GAL-3) were measured by ELISA in 35 patients with symptomatic indolent B-NHL, 41 patients with asymptomatic disease, and 62 healthy controls. Bootstrap t-tests were used to assess the relative differences in biomarker levels between groups. Group differences were visualized using a principal component plot.

Results: Mean plasma endostatin and GDF15 levels were significantly higher in symptomatic and asymptomatic lymphoma patients than in controls. Symptomatic patients had higher mean MMP9 and NGAL than controls.

Conclusions: The finding of increased plasma endostatin and GDF15 in patients with asymptomatic indolent B-NHL suggests that increased angiogenic activity is an early event in indolent B-NHL disease progression.


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How to Cite
Hidman J., Larsson A., Thulin M., & Karlsson T. (2023). Increased plasma endostatin and GDF15 in indolent non-Hodgkin lymphoma. Upsala Journal of Medical Sciences, 128(1).