Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis
Expression of DCC protein in colorectal tumors and its relationship to tumor progression and metastasis
复制标题
DOI：
10.1159/000011954
复制
发表时间：
1999-01-01
期刊：
影响因子：
3.5
通讯作者：
Furukawa, K
中科院分区：
文献类型：
--
作者：
Saito, M;Yamaguchi, A;Furukawa, K
DCC基因在结直肠癌组织中存在杂合性缺失，该杂合性缺失可能与肿瘤转移有关。本研究的目的是检测DCC蛋白在结直肠癌中的表达，并评价其预后价值。23例患者中有16例(66.7%)DCC基因发生等位基因丢失。16例LOH患者癌组织中DCC的表达均低于癌旁正常组织。Western印迹分析显示，所有23例大肠肿瘤组织中该蛋白的表达均低于邻近正常大肠黏膜组织。癌组织中DCC蛋白表达水平明显低于腺瘤组织。免疫组织化学显示DCC蛋白在结直肠癌组织中表达降低。DCC蛋白的表达与组织学类型、静脉侵犯和血行转移密切相关。与DCC蛋白阳性肿瘤相比，DCC蛋白阴性肿瘤患者复发的相对风险更大。DCC蛋白阳性组的5年生存率为91.0%，DCC蛋白阴性组的5年生存率为58.8%，两组比较差异有统计学意义(P<；0.01)。在使用COX回归模型进行的多因素分析中，DCC蛋白的表达是一个独立的预后指标。这些发现表明，DCC表达的降低可能在结直肠癌的进展中起着重要作用，并可能是一个具有预后意义的生物学标志。
A loss of heterozygosity (LOH) at the DCC gene locus was detected in colorectal tumors, and this LOH might be related to metastasis. The aim of this study was to determine DCC protein expression in colorectal cancer and to evaluate its prognostic value. Allelic loss of the DCC locus was observed in 16 of the 23 patients (66.7%). In all 16 patients with LOH, DCC expression was decreased in the cancer tissue compared with the adjacent normal mucosa. All 23 colorectal tumors had decreased expression of this protein relative to the adjacent normal colonic mucosa in Western blot analysis. The levels of DCC protein were significantly lower in cancer tissues than in adenoma tissues. Decreased DCC protein expression was also observed by immunohistochemistry in the colorectal cancer cases. There were significant correlations between DCC protein expression and histologic type, venous invasion, and hematogenous metastasis. Patients with DCC-protein-negative tumors had a greater relative risk of recurrence compared with those whose tumors were DCC protein-positive. The 5-year survival rate was 91.0% in patients with DCC-protein-positive tumors, and 58.8% in those with DCC-protein-negative tumors; these differences between the two groups of patients were significant (p < 0.01). In multivariate analysis using the Cox regression model, DCC protein expression emerged as an independent prognostic indicator. These findings suggested that a decrease in DCC expression may have an important role in the progression of colorectal cancers and may be a biologic marker of prognostic significance.