结缔组织生长因子在结直肠癌组织中的表达及其与患者预后的关系

Expression of connective tissue growth factor in colorectal cancer and its association with prognosis

目的探讨结直肠癌组织中结缔组织生长因子（CTGF）mRNA和蛋白的表达及其与患者临床病理因素及5年生存率的关系。方法采用实时定量PCR技术检测92例结直肠癌及其相应远端正常结肠组织中CTGFmRNA的表达情况，再从中随机选取30对组织进行免疫组织化学检测CTGF蛋白表达．并对该组患者进行生存分析。结果CTGFmRNA在结直肠癌组织中高表达，其CTGF蛋白阳性率73．3％（22／30）高于正常结肠组织的23．3％（7／30）（P〈0．01）。合并淋巴结转移和肿瘤分期为Ⅲ、Ⅳ期者。CTGFmRNA表达水平和蛋白阳性率降低（均P〈0．05）；CTGF蛋白阳性表达率低者浸润深度越深（P〈0．05）。癌组织CTGFmRNA高表达组患者的5年生存率高于低表达组（68.3％比29．3％．P〈0．01）。癌组织CTGFmRNA相对表达水平是患者生存期的独立影响因素（RR=2．960，95％CI：1．49-5．877,P〈0．01），其预测患者预后的敏感性为64．9％，特异性为74．5％。结论CTGF的异常表达与结直肠癌恶性生物学行为有关，CTGF低表达的结直肠癌患者预后不良。

Objective To investigate the expression of connective tissue growth factor （CTGF） in colorectal cancer（CRC） and its association with clinicopathologic parameters and overall survival rate. Methods Fresh tumor tissues and matched distal normal colon tissues were collected from 92 patients diagnosed as CRC by surgical operation. The expression level of CTGF mRNA was quantified by quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue specimens were selected randomly to detect CTGF protein by immunohistochemistry. All the cases were followed up to identify prognostic factors for survival. Results CTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF protein expression tissues （73.3%） was significantly higher than that in the corresponding normal tissues（23.3%, P〈0.01 ）. CTGF expression was lower in patients with lymphatic metastasis or stage Ⅲ/Ⅳ disease （all P〈0.05）. A negative association was also observed between the CTGF protein positive rate and tumor infiltration depth （P〈0.05）. The relative expression of CTGF mRNA in tumor tissues was classified into high and low expression groups. The 5-year cumulative survival rate was lower in patients with low CTGF expression（29.3%） as compared to those with high CTGF expressions（68.3%）（P〈0.01 ）. Cox regression analysis revealed that the relative expression level of CTGF was independent factor of overall survival（RR=2.960, 95%CI： 1.491-1.587, P〈0.01）. ROC curve analysis showed that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year survival were 64.9% and 74.5%, respectively. Conclusions The aberrant expression of CTGF is associated with the malignant biologicalbehaviors of CRC. Low expression of CTGF is associated with worse prognosis of CRC.