Expression and Prognostic Value of CD133, β-catenin, and APC Proteins in Colorectal Carcinoma Tissues
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摘要:
目的 探讨CD133、β-catenin和APC蛋白在结直肠癌发生发展中的作用, 分析三者的表达和临床病理特征与结直肠癌患者预后的关系。 方法 应用组织芯片及免疫组织化学法检测74例结直肠腺瘤、135例结直肠癌及癌旁正常黏膜组织中CD133、β-catenin和APC蛋白的表达; 结合随访资料进行单因素Kaplan-Meier生存分析及多因素Cox回归分析。 结果 CD133在结直肠癌中阳性率为45.9%, 高于腺瘤(9.5%)及癌旁正常黏膜(0, P < 0.05), 其表达与腺瘤不典型增生程度及结直肠癌组织分级具有相关性(P < 0.05);β-catenin胞质/胞核阳性表达在结直肠癌(93.3%)和腺瘤(85.1%), 高于癌旁正常黏膜(14.8%, P < 0.05), β-catenin膜表达缺失率在结直肠癌(45.2%)高于腺瘤(4.1%)及癌旁正常黏膜(5.2%, P < 0.05), 且与淋巴结转移及Dukes分期有关(P < 0.05);APC阳性表达率在癌旁正常黏膜(100%)、腺瘤(90.5%)和结直肠癌(34.8%)呈逐级降低(P < 0.05), 在结直肠癌APC表达缺失组, β-catenin胞质/胞核表达与CD133表达呈正相关(P < 0.05)。单因素和多因素生存分析均筛选出Dukes分期、β-catenin膜表达缺失为影响结直肠癌患者预后的高风险因素及独立预后影响因素(P < 0.05)。 结论 CD133、β-catenin、APC参与了结直肠癌的发生发展, CD133表达与β-catenin及APC之间存在密切联系, 三者的检测对结直肠癌的早期诊断、生物学行为及预后评估有一定意义。 Abstract:Objective The objectives of this study were to investigate the clinical significance ofCD133, β-catenin, and APC protein expression in the tumorigenesis and progression of colorectal carcinoma (CRC) as well as evaluate the relationship between the clinico- pathological characteristics of these proteins and prognosis in CRC patients. Methods The expression levels of CD133, β-catenin, and APC were detected using immunohistochemistry SP (streptavidin peroxidase) assay in tissue microarrays consisting of 135 specimens of CRC and adjacent normal mucosa (ANM) tissues and 74 specimens of colorectal adenoma (CRA) tissues. Clinical follow-up data and survival were assessed using Kaplan - Meier analysis and multivariate Cox regression. Results The positive rates of CD 133 (45.9%) in CRC were significantly higher than those in CRA (9.5%) and ANM (0%) (P < 0.05), and they were related with the degree of dysplasia of CRA and the degree of differentiation of CRC (P < 0.05). The ectopic expression levels of β-catenin in the cytoplasrrdnucleus of CRC (93.3%) and CRA (85.1%) were higher than those in the cytoplasm/nucleus of ANM (14.8%) (P < 0.05). Loss of expression of β-catenin was significantly higher in the cytomembrane of CRC (45.2%) than in those of CRA (4.1%) and ANM (5.2%) (P < 0.05), and it was associated with lymph node metastasis and Dukes stage of CRC (P < 0.05). The positive rates of APC gradually decreased from 100.0% in ANM to 90.5% in CRA to 34.8% in CRC (P < 0.05). The expression of β-catenion in the cytoplasm/nucleus was positively correlated with CD 133 in CRC (P < 0.05), mainly appearing in the group lacking APC expression. Kaplan - Meier analysis and multivariate Cox regression demonstrated that Dukes stage and loss of expression of β-catenin in the cytomembrane were not only high-risk factors in the prognosis of CRC patients hut also independent prognostic factors for low survival in CRC (P < 0.05). Conclusion CD133, β-catenin, and APC may play important roles in the tumorigenesis and progression of CRC. CD133 and β-catenin/APC have intrinsic relationships among them. Their detection may be of value in understanding the early diagnosis of CRC and in evaluating the biological behavior and prognosis of the disease. -
Key words:
- Colorectal carcinoma /
- CD133 /
- β-catenin /
- APC /
- Immunohistochemistry
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图 1 不同结直肠病变组织中CD133、β-catenin和APC蛋白的表达（SP×200）
A1、A2：CD133蛋白在ANM、CRA组织中未见明显表达；A3：CD133蛋白在CRC中表达于细胞膜腺腔面，可见肠黏膜腺体基底部部分细胞着色；B1：β-catenin蛋白在ANM组织中主要表达于细胞膜；B2：β-catenin蛋白在CRA表达于细胞膜和胞质；B3：β-catenin蛋白在CRC表达于细胞质/ 胞核，并伴胞膜表达缺失；C1、C2：APC蛋白在ANM和CRA组织中表达于胞浆；C3：APC蛋白在CRC组织中表达缺失
Figure 1. Expression of CD133, β-catenin and APC protein in the different colorectal tissues(SP×200)
图 2 CRC患者生存分析
A：72例结直肠癌患者总生存率曲线；B：Dukes'分期对生存时间的影响；C：β-catenin膜表达缺失对生存时间的影响；D：CD133高表达对生存时间的影响
Figure 2. Kaplan-Meier curves for the patients with CRC
表 1 CD133、β-catenin和APC蛋白在不同结直肠病变组织中的表达 例（%）
Table 1. Expression of CD133, β-catenin and APC protein in the different colorectal tissues
表 2 CRC和CRA组织中β-catenin与APC、CD133蛋白表达的相关系数
Table 2. Correlations of β-catenin expression to APC, CD133 expression in CRC and CRA
表 3 APC不同表达情况下CRC组织中CD133与β-catenin蛋白表达的相关系数
Table 3. Correlations of β-catenin expression to CD133 expression in the variety of APC expression of CRC
表 4 CRC患者Cox比例风险模型多因素回归分析结果
Table 4. Multivariable Cox proportional hazards regression analysis of patients with CRC
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