目的 检测肿瘤抑制基因PDCD4在大肠癌组织中的表达,探讨其在大肠癌发生发展中的作用及对预后的影响.方法 应用western印迹分析和免疫组织化学染色方法,检测了大肠癌及癌旁的正常组织中PDCD4的表达,观察其与大肠癌患者临床病理学参数之间的关系,并分析其对预后的影响.结果 Western印迹分析和免疫组化染色均显示,与癌旁的正常大肠组织相比,癌组织中PDCD4的表达明显下降.免疫组化染色显示,在65例大肠癌组织中,高、中、低分化腺癌分别占49.2%(32/65)、33.9%(22/65)和16.9%(11/65).在高、中、低分化腺癌中,PDCD4(+)表达率分别为81.3%(26/32)、50.0%(11/22)和18.2%(2/11).相关分析显示,PDCD4的表达水平与大肠癌的程度密切相关,分化越差,表达越低.Kaplan-Meier生存分析显示,PDCD4的表达水平与预后有关,PDCD4阴性者预后差.应用Cox比例风险模型进行多因素分析,结果显示,本组资料中,Dukes分期、PDCD4表达水平以及术后是否进行化疗影响大肠癌的预后.结论 本研究显示,大肠癌组织中PDCD4的表达下降,并与肿瘤的分化程度和不良预后相关.作为一种肿瘤抑制基因,PDCD4可能在大肠癌的发生发展中起重要作用.PDCD4还可能作为有效的预后因子,有助于判断预后.%[Objective] To examine the expression of programmed cell death 4(PDCD4) in human colorectal carcinoma (CRC) and investigate its prognotic effect. [Methods] PDCD4 expression in 5 fresh specimens of CRC and the corresponding non cancerous tissues was detected by western blot with PDCD4 specific antibody. Immunohisto-chemistry analysis was used to examine the expression of PBCD4 in 65 paraffin embedded specimens of CRC and the adjuvant normal tissues. Correlations of PDCD4 expression with clinico pathological data were analyzed. [Results] The expression of PDCD4 was significantly lower in all 5 fresh CRC tissues than that in non-cancerous tissues detected by western blot. Compared with adjuvant normal tissues (＞80% of positive cells) examined by immuno-histochemistry, low PDCD4 expression was shown in all CRC tissues (＜30% of positive cells in 26 cases and 30% ～80% of positive cells in 39 cases). Among 65 cases of CRCs, the well, moderately and poorly differentiated cancers were 49.2% (32/65), 33.9% (22/65) and 16.9% (11/65) respectively. The positive rate of PDCD4 expression was 81.3% (26/32) in well differentiated cancer, significantly higher than that in moderately and poorly differentiated cancer, which were 50% (11/22) and 18.2% (2/11) respectively, indicating that low PDCD4 level was associated with histological grade (P ＜0.01). The absence of PDCD4 protein expression was strongly linked to poor prognosis, revealed by Kaplan-Meier statistical analysis (P ＜0.05), with the mean survival time for patients with PDCD4 (+) tumors reaching 57 months compared with 36 months in patients with PDCD4 (-) tumors. A multivariate analysis of maximum likelihood estimates using the Cox's proportional hazard risk model demonstrated that PDCD4 expression, Dukes stage and postoperative chemotherapy were associated with the prognosis. [Conclusions] Our study indicates that the expression of PDCD4 protein is down-regulated in human CRC, and this down-regulation is correlated with histological differentiation and poor prognosis. PDCD4 may play an important role in occurrence and development of CRC and may be a useful prognostic factor.
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