Swierzko Anna St, Szala Agnieszka, Sawicki Sambor, Szemraj Janusz, Sniadecki Marcin, Sokolowska Anna, Kaluzynski Andrzej, Wydra Dariusz, Cedzynski Maciej
Laboratory of Immunobiology of Infections, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232, Lodz, Poland.
Cancer Immunol Immunother. 2014 Nov;63(11):1129-40. doi: 10.1007/s00262-014-1579-y. Epub 2014 Jul 20.
Mannose-Binding Lectin (MBL) is a serum pattern recognition molecule, able to activate complement in association with MASP proteases. Serum levels of MBL and MASP-2, activities of MBL-MASP complexes, single nucleotide polymorphisms of the MBL2 and MASP2 genes and/or their specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary ovarian cancer (OC) and compared with 197 controls (C), encompassing both patients with benign ovarian tumours (n = 123) and others with no ovarian pathology (n = 74). MBL deficiency-associated genotypes were more common among OC patients than among controls. The O/O group of genotypes was associated with ovarian cancer (OR 3.5, p = 0.02). In A/A homozygotes, MBL concentrations and activities were elevated in the OC group and correlated with C-reactive protein. Moreover, high MBL serum levels were associated with more advanced disease stage. No differences in distribution of the MASP2 +359 A>G (D120G) SNP or MASP-2 serum levels were found between cancer patients and their controls. However, the highest frequency of the A/G (MASP2) and LXA/O or O/O (MBL2) genotypes was found among OC patients with tumours of G1-2 grade (well/moderately differentiated). Furthermore, MBL deficiency-associated genotypes predicted prolonged survival. None of the parameters investigated correlated with CA125 antigen or patients' age. The local expression of MBL2 and MASP2 genes was higher in women with ovarian cancer compared with controls. It is concluded that the expression of MBL and MASP-2 is altered in ovarian cancer, possibly indicating involvement of the lectin pathway of complement activation in the disease.
甘露糖结合凝集素(MBL)是一种血清模式识别分子,能够与MASP蛋白酶协同激活补体。对128例原发性卵巢癌(OC)患者的血清MBL和MASP-2水平、MBL-MASP复合物活性、MBL2和MASP2基因的单核苷酸多态性及/或其在卵巢组织切片中的特定mRNA表达进行了研究,并与197名对照者(C)进行比较,对照者包括患有良性卵巢肿瘤的患者(n = 123)和无卵巢病变的其他人(n = 74)。与MBL缺乏相关的基因型在OC患者中比在对照者中更常见。O/O基因型组与卵巢癌相关(比值比3.5,p = 0.02)。在A/A纯合子中,OC组的MBL浓度和活性升高,且与C反应蛋白相关。此外,高MBL血清水平与更晚期的疾病阶段相关。在癌症患者及其对照者之间,未发现MASP2 +359 A>G(D120G)单核苷酸多态性的分布或MASP-2血清水平存在差异。然而,在G-1至2级(高分化/中分化)肿瘤的OC患者中,发现A/G(MASP2)和LXA/O或O/O(MBL2)基因型的频率最高。此外,与MBL缺乏相关的基因型预示着生存期延长。所研究的参数均与CA125抗原或患者年龄无关。与对照者相比,卵巢癌女性中MBL2和MASP2基因的局部表达更高。结论是,卵巢癌中MBL和MASP-2的表达发生改变,这可能表明补体激活的凝集素途径参与了该疾病。