Department of Medical Science, Uppsala University, Uppsala, Sweden.
Centre for Clinical Research Västmanland, Västmanland County Hospital, Uppsala University, Uppsala, Sweden.
Ups J Med Sci. 2023 May 9;128. doi: 10.48101/ujms.v128.9392. eCollection 2023.
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.
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.
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.
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.
非霍奇金淋巴瘤（NHL）中微血管密度的增加与更晚期的疾病和不利的总生存率相关，这表明血管生成对于疾病进展很重要。然而，针对 NHL 患者的抗血管生成药物的研究通常未显示出有利的结果。本研究旨在探讨惰性 B 细胞来源的 NHL（B-NHL）患者的血浆中是否存在一组与血管生成相关的蛋白水平升高，并探讨无症状与有症状疾病患者之间的水平是否存在差异。
通过 ELISA 法测量 35 例有症状的惰性 B-NHL 患者、41 例无症状疾病患者和 62 名健康对照者的生长分化因子 15（GDF15）、内皮抑素、基质金属蛋白酶 9（MMP9）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、长五聚蛋白 3（PTX3）和半乳糖凝集素 3（GAL-3）的血浆水平。使用 bootstrap t 检验评估组间生物标志物水平的相对差异。使用主成分图可视化组间差异。
有症状和无症状淋巴瘤患者的平均血浆内皮抑素和 GDF15 水平明显高于对照组。有症状的患者的 MMP9 和 NGAL 平均值高于对照组。
在无症状的惰性 B-NHL 患者中发现血浆内皮抑素和 GDF15 升高，提示血管生成活性增加是惰性 B-NHL 疾病进展的早期事件。
