E-选择素及其配体表达对肝癌转移的临床意义

目的 探讨E-选择索(E-selectin)及其配体在肝癌细胞与内皮细胞黏附中的作用和二者表达的临床意义;并筛选可能阻断黏附作用的药物. 方法 收集78例肝细胞癌患者的临床资料,采用免疫组织化学方法检测E-selectin、sLeX、sLeA、CD44v6的表达情况,按临床特征分组并比较各组E-selectin、sLeX、sLeA、CD44v6的阳性表达率差异.体外实验采用实时荧光定量PCR检测E-selectin和细胞间黏附分子(ICAM)-1在ED25、ECV304两种内皮细胞中的表达;黏附实验检测肝癌细胞HepG2与ED25、ECV304两种内皮细胞的黏附活性,并检测不同药物对黏附作用的影响.对临床资料数据采用χ2检验、Kaplan-Meier生存分析与Wilcoxon检验;对体外实验计量数据进行方差分析.结果 E-selectin在肝癌病灶内血管内皮细胞中的阳性表达率为70.51%,sLeX、sLeA、CDJ44v6在肝癌细胞中的阳性表达率分别为64.10%、69.23%、62.90%.sLeX、sLeA、CD44v6表达阴性患者的平均生存期显著长于阳性患者(P值均<0.05).有门静脉癌栓、术前肝外转移、卫星病灶、术后3个月内复发各组E-selectin、sLeX、sLeA的阳性表达率差异均有统计学意义(P值均<0.05);而肿瘤大小、血清AFP水平均与E-selectin、sLeX、sLeA的阳性表达率无相关性;病理分级Ⅲ～Ⅳ级组与Ⅰ～Ⅱ级组的E-selectin和CD44v6的阳性表达率差异均有统计学意义(P值均<0.05).CD44v6的表达特点是术后3个月内复发者有较高的阳性率,有卫星灶者阳性率也较高.E-selectin和ICAM-1可高表达于活化后的ED25和ECV304细胞;且能介导HepG2细胞与ED25和ECV304细胞的黏附,地塞米松,丹参酮ⅡA都具有较强的抗黏附能力,且抗黏附作用随着浓度的增加而增强.结论 E-selectin、sLeX.sLeA、CD44v6的表达与患者的预后,门静脉癌栓等临床特征密切相关,可作为临床预后和术后早期复发的评估依据.E-selectin、ICAM-1及其配体可增强肝癌细胞与内皮细胞的黏附,促进肝癌转移;地塞米松、丹参酮ⅡA可阻断其黏附作用.

Effects of E-selectin and their legends on the adhesive metastsis of hepatocellular carcinoma

Objective To explore the effects of E-selectin, ICAM-1 and their legends on the adhesive metastsis of hepatocellular carcinoma (HCC), and to select possible anti-adhesion drugs for hepatocelluar carcinoma metastasis. Methods 78 HCC patients were analyzed with the correlation of clinical features to the expression levels of E-selectin, sLeX, sLeA and CD44v6 in the tumor tissue. The adhesion between HepG2 and endothelial cell lines was examined by solid phase adhesion assay in vitro. Two kinds of drugs were accessed for their anti-adhesion ability. Results The positive rate of E-selectin in vascular endothelia cells adjacent to cancer nest is 70.51 %, and which of sLeX, sLeA, CD44v6 within tumor cells is 64.10%, 69.23%,62.90% respectively. The patients' life span is closely related with the positive expression of sLeX, sLeA, CD44v6 (P = 0.008,0.001,0.022). The positive expression of E-selectin, sLeX and sLeA is significantly correlated to portal vein tumor thrombus (PVTT), preoperative extrahepatic metastasis, and satellite foci, but not to the size of tumor and AFP. The level of CD44v6 expression is significantly correlated to patient's survival time. The expression levels of E-selectin and ICAM-1 are remarkably higher after ED25 and ECV304 cell lines be activated. Meanwhile the adhesive ability of HepG2 to endothelial cell is mediated. Dexamethasone, tanshinone HA are able to block this adhesion at low concentration. Conclusions The expression levels of E-selectin, sLeX, sLeA and CD44v6 are closely correlated with clinical features. E-selectin, ICAM-1 and their legends are important molecules of hepatocellular carcinoma and endothelial cells to tumor adhesive metastasis. Dexamethasone, tanshinone II A can be hopefully used as anti-adhesion drugs.