Expression of sialyl Lewisa relates to poor prognosis in cholangiocarcinoma
Expression of sialyl Lewisa relates to poor prognosis in cholangiocarcinoma
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DOI：
10.3748/wjg.v11.i2.249
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发表时间：
2005-01-14
影响因子：
4.3
通讯作者：
Wongkham, Sopit
中科院分区：
文献类型：
--
作者：
Juntavee, Apa;Sripa, Banchob;Wongkham, Sopit
目的：高水平的血清唾液酸刘易斯（a）（sLe（a））常见于胆管癌（CCA）患者，并被认为是CCA的血清标志物。然而，这种抗原在CCA中的意义尚不清楚。方法：采用免疫组化SP法检测77例肿块型CCA和33例导管周围浸润型CCA中sLe（a）的表达，分析sLe（a）在CCA中表达的临床意义。结果：sLe（a）在60%的CCA肿瘤组织中表达异常，在10%的CCA肿瘤组织中表达异常。sLe（a）蛋白表达频率与肿块型CCA（P = 0.041）、高分化组织学分级（P = 0.029）和血管浸润（P = 0.030）有关。sLe（a）表达阳性者的预后（21.28wk，95% CI = 16.75- 25.81wk）显著低于sLe（a）表达阴性者（37.30wk，95% CI = 27.03- 47.57wk）（P < 0.001）。校正所有协变量后的多变量分析显示，sLe（a）阳性患者的死亡风险是sLe（a）阴性患者的2.3倍（P < 0.001）。使用体外粘附和移行测定证明了sLe（a）在血管侵袭中的作用。高表达sLe（a）的人CCA细胞系KKU-M213与IL-1 β激活的人脐静脉内皮细胞的粘附和迁移率高于不表达sLe（a）的细胞系KKU-100（P < 0.001）。结论：sLe（a）表达在CCA中的临床意义及对CCA预后的不利影响。sLe（a）在血管侵袭中的作用可能导致不良预后，这得到体外粘附和迁移研究的支持。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
AIM: High levels of serum sialyl Lewis(a) (sLe(a)) are frequently found in cholangiocarcinoma (CCA) patients and have been suggested to be a serum marker for CCA. However, the significance of this antigen in CCA is unknown. In this study, the clinical significance of sLe(a) expression in CCA tissues and the possible role of sLe(a) in vascular invasion in vitro were elucidated.METHODS: Expression of sLe(a) in tumor tissues of 77 patients with mass-forming CCA and 33 with periductal infiltrating CCA was determined using immunohistochemistry. The in vitro assays on adhesion and transmigration of CCA cells to human umbilical vein endothelial cells were compared between CCA cell lines with and without sLe(a) expression.RESULTS: sLe(a) was aberrantly expressed in 60% of CCA tumor tissues. A significant relationship was found between the frequency of sLe(a) expression and the mass-forming type CCA (P = 0.041), well differentiated histological grading (P = 0.029), and vascular invasion (P = 0.030). Patients with positive sLe(a) expression had a significantly poorer prognosis (21.28 wk, 95% CI = 16.75-25.81 wk) than those negative for sLe(a) (37.30 wk, 95% CI = 27.03-47.57 wk) (P < 0.001). Multivariate analysis with adjustment for all covariates showed that patients positive for sLe(a) possessed a 2.3-fold higher risk of death than patients negative for sLe(a) (P < 0.001). The role of sLe(a) in vascular invasion was demonstrated using in vitro adhesion and transmigration assays. KKU-M213, a human CCA cell-line with a high expression of sLe(a), adhered and transmigrated to IL-1 beta-activated endothelial cells of the human umbilical vein more than KKU-100, the line without sLe(a) expression (P < 0.001). These processes were significantly diminished when the antibodies specific to either sLe(a) or E-selectin were added to the assays (P < 0.001).CONCLUSION: This study demonstrates the clinical significance of sLe(a) expression in vascular invasion, and an unfavorable outcome in CCA. The role of sLe(a) in vascular invasion which may lead to poor prognosis is supported by the in vitro adhesion and transmigration studies. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.