结直肠癌组织δ-catenin表达与临床病理因素及预后相关性分析

Correlation betweenδ-catenin expression and clinicopathological factors as well as prognosis in colorectal cancer

目的:探讨δ-catenin在结直肠癌组织中的表达与临床病理参数及预后关系。方法:应用免疫组织化学法检测2004-04-15-2010-04-15中国医科大学附属盛京医院病理结直肠癌标本110例及正常结直肠组织标本(外伤等非肿瘤原因肠切除标本)15例中δ-catenin蛋白的表达,其中70例有完整的术后随访资料,40例有配对的转移淋巴结标本。应用Realtime PCR和蛋白质印迹法定量比较30例结直肠癌与癌旁结直肠黏膜中δ-catenin的mRNA和蛋白表达差异。结果:免疫组织化学检测结果显示,在结直肠癌组织中δ-catenin呈阳性表达68.18%(75/110),而在正常结直肠黏膜上皮细胞中仅呈现较弱表达(5例)或不表达(10例)。δ-catenin的阳性表达与结直肠癌患者的病灶所在部位(χ2=0.163,P=0.686)、肿瘤大小(χ2=2.386,P=0.122)、年龄(χ2=0.112,P=0.738)和性别(χ2=0.082,P=0.775)均无关,而与分化程度(χ2=2.393,P=0.012)、TNM分期(χ2=6.320,P=0.012)和淋巴结转移(χ2=5.771,P=0.016)密切相关。70例有完整随访资料的结直肠癌患者5年生存率为64.29%(45/70),δ-catenin阳性表达的患者5年生存率为51.11%(23/45),显著低于阴性表达者的88.00%(22/25),P=0.005。Cox模型多因素分析结果显示,δ-catenin阳性表达很可能是影响结直肠癌患者预后的独立危险因素,P=0.031。Real-time PCR检测结果显示,结直肠癌组织δ-catenin mRNA表达水平为22.61±2.57,显著高于正常肠黏膜组织的3.25±0.88,两者比较差异有统计学意义,t=7.137,P<0.001。蛋白质印迹法检测结果显示,结直肠癌组织δ-catenin蛋白表达量为0.95±0.11,显著高于正常肠黏膜组织的0.32±0.07,两者比较差异有统计学意义,t=7.772,P<0.001。结论:结直肠癌组织中δ-catenin过度表达,与低分化、晚分期、淋巴结转移和不良预后密切相关,提示δ-catenin可能参与了结直肠癌的恶性进展和转移。

OBJECTIVE：To explore the expression of δ-catenin in human colorectal cancer（CRC） ,and analyze the relationship between δ-eatenin expression and clinical features as well as prognostic significance in CRC. METHODS： Totally 110 cases of coloreetal cancer specimens and 15 cases of traumatic colorectal tissues were collected from 2004-04-15 to 2010-04-15 in Shengjing Hospital of China Medical University. Expression of δ-catenin in 110 cases of CRC（including 40 cases of paired lymph nodes metastases and 70 cases with complete follow-up records） was detected by immunohisto- chemistry, mRNA and protein levels in 30 fresh tissues were detected by Real-time PCR and Immunoblotting. RESULTS： The immunohistochemistry results showed that δ-catenin was weakly expressed in 5 cases,and even absent in 10 cases of normal colorectal mucosa epithelial cells. No correlation was found between 3-catenin expression and primary site（x2 = 0.163,P=0. 686） ,tumor size（x2=2.386,P=0.122）,age（z=0.112,P=0.738） and sex（x2=0.082,P=0.775）.The positive expression of 3-catenin in CRC was 68. 18% （75/110）,it was correlated with differentiation （X2 = 2. 393, P= 0. 012）,TNM stage （X2 =6. 320 ,P= 0. 012） and lymph node metastasis （X2 = 5. 771, P= 0. 016）. The CRC-related survival rate was 64.29 % （45/70）, while the rate was 51.11 % （23/45） in 8-catenin positive group and 88.00% （22/25） in δ-catenin negative group,P= 0. 005. A multivariate Cox regression analysis showed that expression of δ-catenin might he an independent prognostic factor in CRC,P= 0. 031. The Real-time PCR results showed that the levels of δ-catenin mRNA in CRC tissues （22. 61 ± 2. 57） were significantly higher than that in normal tissues （3. 25 ±0.88） （t= 7. 137, P〈 0. 001）. The immunoblotting results showed that the δ-eatenin protein levels in CRC tissues （0.95 ± 0.11） were significantly higher than that in normal tissues （0.32±0.07） （t= 7. 772, P〈0. 001）. CONCLUSIONS： δ-catenin is overexpresssed in CRC specimens,and it is closely related to poor differentiation, advanced stage,lymph node metastasis and poor prognosis. These results suggest that δ-catenin might participate in the malignant progression and metastasis of CRC.