Perez Carlos A, Ravindranath Mepur H, Soh Daniel, Gonzales Alexandra, Ye Wei, Morton Donald L
Department of Glycoimmunotherapy, Roy E. Coats Research Laboratories, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California 90404-2302, USA.
Cancer J. 2002 Sep-Oct;8(5):384-94. doi: 10.1097/00130404-200209000-00009.
Gangliosides are tumor-associated antigens with many biologic functions, including complex interactions with cytokines and other modulators of the immune system. Serum total ganglioside level may be an ideal surrogate marker to predict tumor burden and response to treatment. Antibodies produced against tumor gangliosides may help predict survival. The purpose of this study is to determine whether the serum total ganglioside levels might predict the tumor burden in patients with soft tissue sarcoma, and whether the augmented anti-ganglioside immunoglobulin M (IgM) response might reflect the clinical outcome of these patients.
Serum TG levels were measured in the cryopreserved sera by estimating lipid-associated sialic acids from 97 patients before surgical resection of soft tissue sarcoma and from 39 age- and gender-matched healthy volunteers. All sera were analyzed for IgM titers (expressed natural log) by enzyme-linked immunosorbent assay against eight gangliosides (GM1, GM2, GM3, GD3, GD2, GD1a, GD1b, and GT1b). Cox regression was used for univariate and multivariate analyses of the variables affecting progression-free and overall survival.
Serum TG levels were higher in soft tissue sarcoma patients than in healthy individuals (21.8 + 7.7 vs 16.1 + 2.7 mg/dL; P = 0.001). Larger tumors, high histologic grade, and more advanced stage of disease correlated with higher serum total ganglioside levels (P < 0.05). Anti-ganglioside titers to GM3, GD2, and GT1b were significantly higher in patients with soft tissue sarcoma, whereas anti-GD1a and GD1b titers were significantly higher in healthy subjects. The titers of antibodies against GM1, GM2, and GD3 in patients with soft tissue sarcoma were comparable to those of the healthy individuals. When compared with healthy controls, patients with low-grade tumors had higher titers of anti-GT1b, anti-GM3, and anti-GD2 antibodies, and patients with high-grade tumors had higher titers of anti-GT1b and anti-GD2 antibodies. These data suggest that the predominant gangliosides expressed by sarcomas may include GT1b and GD2. In addition, low-grade tumors may express an immunogenic species of GM3. On both univariate and multivariate analyses, augmented anti-GD1a IgM titers, age > 50 years, and retroperitoneal location were predictive of decreased overall survival, whereas augmented anti-GT1b titers were predictive of improved overall survival.
Serum TG level may be a useful marker of tumor burden and response to treatment for soft tissue sarcoma. Anti-GD1a and anti-GT1b IgM titers predicted survival and may be of therapeutic and prognostic value in the management of soft tissue sarcoma.
神经节苷脂是肿瘤相关抗原，具有多种生物学功能，包括与细胞因子及免疫系统的其他调节因子发生复杂相互作用。血清总神经节苷脂水平可能是预测肿瘤负荷及治疗反应的理想替代标志物。针对肿瘤神经节苷脂产生的抗体可能有助于预测生存情况。本研究的目的是确定血清总神经节苷脂水平是否可预测软组织肉瘤患者的肿瘤负荷，以及抗神经节苷脂免疫球蛋白M（IgM）反应增强是否可反映这些患者的临床结局。
通过估算脂质相关唾液酸，对97例软组织肉瘤患者手术切除前的冷冻血清及39例年龄和性别匹配的健康志愿者的血清进行血清总神经节苷脂（TG）水平检测。采用酶联免疫吸附测定法分析所有血清针对8种神经节苷脂（GM1、GM2、GM3、GD3、GD2、GD1a、GD1b和GT1b）的IgM滴度（以自然对数表示）。使用Cox回归对影响无进展生存期和总生存期的变量进行单因素和多因素分析。
软组织肉瘤患者的血清TG水平高于健康个体（21.8 + 7.7 vs 16.1 + 2.7 mg/dL；P = 0.001）。肿瘤体积较大、组织学分级高及疾病分期较晚与血清总神经节苷脂水平较高相关（P < 0.05）。软组织肉瘤患者针对GM3、GD2和GT1b的抗神经节苷脂滴度显著更高，而健康受试者中抗GD1a和GD1b滴度显著更高。软组织肉瘤患者针对GM1、GM2和GD3的抗体滴度与健康个体相当。与健康对照相比，低级别肿瘤患者的抗GT1b、抗GM3和抗GD2抗体滴度更高，高级别肿瘤患者的抗GT1b和抗GD2抗体滴度更高。这些数据表明，肉瘤表达的主要神经节苷脂可能包括GT1b和GD2。此外，低级别肿瘤可能表达具有免疫原性的GM3。在单因素和多因素分析中，抗GD1a IgM滴度升高、年龄>50岁及腹膜后位置可预测总生存期降低，而抗GT1b滴度升高可预测总生存期改善。
血清TG水平可能是软组织肉瘤肿瘤负荷及治疗反应的有用标志物。抗GD1a和抗GT1b IgM滴度可预测生存情况，在软组织肉瘤的管理中可能具有治疗和预后价值。
