Bono Petri, Teerenhovi Lasse, Joensuu Heikki
Department of Oncology, Helsinki University Central Hospital, Finland.
Cancer. 2003 Jun 1;97(11):2767-75. doi: 10.1002/cncr.11399.
Endostatin is a cleaved fragment of collagen Type XVIII and has antiangiogenic activity. The clinical significance of circulating, soluble endostatin (S-endostatin) is not known.
Pretreatment S-endostatin and serum vascular endothelial growth factor (S-VEGF) levels were measured in 143 patients with non-Hodgkin lymphoma (NHL) using competitive enzyme immunoassays and were compared with the levels from a control group (n = 24 participants).
S-endostatin levels varied widely from 4.5 ng/mL to 116 ng/mL (median, 29.6 ng/mL), and the median level was higher in patients with NHL compared with patients in the control group (16.4 ng/mL; P = 0.05). High S-endostatin levels were associated with advanced disease stage (P < 0.0001) and high serum VEGF levels at diagnosis (P = 0.017). The median 5-year survival rate for patients who had S-endostatin concentrations within the highest tertile (> 36.0 ng/mL) was only 34% compared with 57% in patients who had lower S-endostatin levels (P = 0.019). A high S-endostatin level also was associated with a poor outcome in patients with large cell diffuse and immunoblastic lymphoma, which was the largest subgroup within the series (n = 60 patients). Patients who had high pretreatment levels of both S-VEGF and S-endostatin had particularly poor outcomes. High S-endostatin levels had an independent, adverse influence on survival it was entered as a factor into a multivariate analysis together with the factors included in the International Prognostic Index (relative risk, 1.80; 95% confidence interval, 1.08-2.98; P = 0.0024).
High pretreatment levels of S-endostatin are associated with high serum VEGF levels and poor survival in patients with NHL. Prospective studies are warranted to establish the clinical value of longitudinal S-endostatin measurements.
内皮抑素是ⅩⅧ型胶原蛋白的裂解片段，具有抗血管生成活性。循环可溶性内皮抑素（S-内皮抑素）的临床意义尚不清楚。
采用竞争性酶免疫测定法检测143例非霍奇金淋巴瘤（NHL）患者治疗前的S-内皮抑素和血清血管内皮生长因子（S-VEGF）水平，并与对照组（n = 24名参与者）的水平进行比较。
S-内皮抑素水平在4.5 ng/mL至116 ng/mL之间广泛波动（中位数为29.6 ng/mL），NHL患者的中位数水平高于对照组患者（16.4 ng/mL；P = 0.05）。高S-内皮抑素水平与疾病晚期（P < 0.0001）及诊断时高血清VEGF水平（P = 0.017）相关。S-内皮抑素浓度处于最高三分位数（> 36.0 ng/mL）的患者5年生存率中位数仅为34%，而S-内皮抑素水平较低的患者为57%（P = 0.019）。高S-内皮抑素水平还与大细胞弥漫性和免疫母细胞性淋巴瘤患者的不良预后相关，这是该系列中最大的亚组（n = 60例患者）。治疗前S-VEGF和S-内皮抑素水平均高的患者预后尤其差。高S-内皮抑素水平对生存有独立的不良影响，将其作为一个因素与国际预后指数中的因素一起纳入多变量分析（相对风险，1.80；95%置信区间，1.08 - 2.98；P = 0.0024）。
NHL患者治疗前高S-内皮抑素水平与高血清VEGF水平及不良生存相关。有必要进行前瞻性研究以确定纵向S-内皮抑素测量的临床价值。
