Zehnder Aina, Fisch Urs, Hirt Andreas, Niggli Felix K, Simon Arne, Ozsahin Hulya, Schlapbach Luregn J, Ammann Roland A
Department of Pediatrics, University of Bern, Bern, Switzerland.
Pediatr Blood Cancer. 2009 Jul;53(1):53-7. doi: 10.1002/pbc.22028.
Mannose-binding lectin (MBL) and MBL-associated serine protease-2 (MASP-2) are key components of the lectin pathway of complement activation. Their serum concentrations show a wide interindividual variability. This study investigated whether the concentration of MBL and MASP-2 is associated with prognosis in pediatric patients with cancer.
In this retrospective multicenter study, MBL and MASP-2 were measured by commercially available ELISA in frozen remnants of serum taken at diagnosis. Associations of overall survival (OS) and event-free survival (EFS) with MBL and MASP-2 were assessed by multivariate Cox regression accounting for prognostically relevant clinical variables.
In the 372 patients studied, median serum concentration of MBL was 2,808 microg/L (range, 2-10,060) and 391 microg/L (46-2,771) for MASP-2. The estimated 4-year EFS was 0.60 (OS, 0.78). In the entire, heterogeneous sample, MBL and MASP-2 were not significantly associated with OS or EFS. In patients with hematologic malignancies, however, higher MASP-2 was associated with better EFS in a significant and clinically relevant way (hazard ratio per tenfold increase (HR), 0.22; 95% CI, 0.09-0.54; P = 0.001). This was due to patients with lymphoma (HR, 0.11; 95% CI, 0.03-0.47; P = 0.003), but less for those with acute leukemia (HR, 0.35; 95% CI, 0.11-1.15; P = 0.083).
In this study, higher MASP-2 was associated with better EFS in pediatric patients with hematologic malignancies, especially lymphoma. Whether MASP-2 is an independent prognostic factor affecting risk stratification and anticancer therapy needs to be assessed in prospective, disease-specific studies.
甘露糖结合凝集素(MBL)和MBL相关丝氨酸蛋白酶-2(MASP-2)是补体激活凝集素途径的关键成分。它们的血清浓度在个体间存在很大差异。本研究调查了MBL和MASP-2的浓度与儿童癌症患者预后是否相关。
在这项回顾性多中心研究中,通过市售酶联免疫吸附测定法(ELISA)检测诊断时采集的血清冷冻残余物中的MBL和MASP-2。通过多变量Cox回归评估总生存期(OS)和无事件生存期(EFS)与MBL和MASP-2的相关性,并考虑预后相关的临床变量。
在研究的372例患者中,MBL的血清中位浓度为2808μg/L(范围为2 - 10060),MASP-2为391μg/L(46 - 2771)。估计的4年EFS为0.60(OS为0.78)。在整个异质性样本中,MBL和MASP-2与OS或EFS均无显著相关性。然而,在血液系统恶性肿瘤患者中,较高的MASP-2与更好的EFS具有显著且临床相关的关联(每增加十倍的风险比(HR)为0.22;95%置信区间为0.09 - 0.54;P = 0.001)。这主要是由于淋巴瘤患者(HR为0.11;95%置信区间为0.03 - 0.47;P = 0.003),而急性白血病患者的相关性较弱(HR为0.35;95%置信区间为0.11 - 1.15;P = 0.083)。
在本研究中,较高的MASP-2与血液系统恶性肿瘤儿童患者,尤其是淋巴瘤患者更好的EFS相关。MASP-2是否为影响风险分层和抗癌治疗的独立预后因素,需要在前瞻性、疾病特异性研究中进行评估。