Smorodin Eugeniy-P, Kurtenkov Oleg-A, Sergeyev Boris-L, Kodar Kristel-E, Chuzmarov Valentin-I, Afanasyev Vladimir-P
Department of Oncology and Immunology, National Institute for Health Development, Hiiu 42, Tallinn 11619, Estonia.
World J Gastroenterol. 2008 Jul 21;14(27):4352-8. doi: 10.3748/wjg.14.4352.
To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic alphaGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer.
Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages I-IV without distant metastases were subjected to follow-up. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment.
In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and alphaGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cut-off value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (c2 = 3.89, all patients; c2 = 5.34, patients without regional lymph node metastases; P < 0.05). The percentage of patients with a tumor in stage I, whose mean anti-TF IgG level remained above the cut-off value (1.26), was significantly higher than that of patients with the cancer in stages III-IV (c2 = 4.71, gastric cancer; c2 = 4.11, gastrointestinal cancer; P < 0.05). The correlation was observed to exist between the level of anti-TF IgG and the count of lymphocytes (r = 0.517, P < 0.01), as well as between the level of anti-Tn IgG and that of serum CA 19-9 (r = 0.481, P < 0.05). No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed.
The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stage- and morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.
研究肿瘤切除对血清中肿瘤相关的汤姆森 - 弗里德赖希(TF)、Tn碳水化合物表位及异种αGal IgG抗体水平的影响,阐明随访期间该水平的变化及其与胃肠道癌肿瘤分期、形态以及血液参数值的关系。
对60例I - IV期无远处转移的胃癌患者和34例结直肠癌患者进行随访。采用合成聚丙烯酰胺(PAA)糖缀合物,通过酶联免疫吸附测定(ELISA)法测定血清中抗体水平。使用自动化设备进行生化和血液学分析。
在胃肠道癌中,与术前水平相比,G3肿瘤切除后TF抗体水平显著升高(u = 278.5,P < 0.05)。手术后,大多数胃癌患者的TF和Tn抗体水平升高(符号检验,分别为20比8,P < 0.05和21比8,P < 0.05)。在胃肠道癌中,大多数G3肿瘤患者术后TF、Tn和αGal抗体水平升高(符号检验,分别为22比5,P < 0.01;19比6,P < 0.05;24比8,P < 0.01),但G1 + G2切除肿瘤患者的升高不显著。术后随访显示,消化道G3切除肿瘤患者中抗TF IgG平均水平高于临界值(1.53)的患者百分比显著高于G1 + G2切除肿瘤患者(χ² = 3.89,所有患者;χ² = 5.34,无区域淋巴结转移患者;P < 0.05)。I期肿瘤患者中抗TF IgG平均水平仍高于临界值(1.26)的患者百分比显著高于III - IV期癌症患者(χ² = 4.71,胃癌;χ² = 4.11,胃肠道癌;P < 0.05)。观察到抗TF IgG水平与淋巴细胞计数之间存在相关性(r = 0.517,P < 0.01),抗Tn IgG水平与血清CA 19 - 9水平之间也存在相关性(r = 0.4,81,P < 0.05)。在包括抗TF IgG水平高的15例患者中,用TF - PAA进行皮肤试验激发均未观察到阳性迟发型超敏反应。
手术可使大多数患者,尤其是胃肠道G3肿瘤患者的抗碳水化合物IgG水平升高。随访表明,手术后早期癌症患者术前较低的TF抗体水平可能会大幅升高,但晚期则保持较低水平。分期和形态依赖性免疫抑制影响TF抗体反应,可能是对TF抗原免疫无反应的原因之一。