ErbB-2、PAK1及VEGF在大肠癌中的关系及其意义研究

Relationship and significance of ErbB-2,PAK1 and VEGF in colorectal carcinoma

目的探讨ErbB-2、PAK1和VEGF在大肠癌中的表达与相关性以及三者与大肠癌临床病理特征之间的关系。方法选取结直肠癌根治术后病理检测确诊为大肠癌的组织标本共48例,分为三组:肠癌组织组(48例)、癌旁组织组(21例)及远癌组织组(12例)。分别采用western blot法和RT-PCR法检测ErbB-2、PAK1及VEGF在各组中的蛋白表达及基因表达,并分析三者表达的相关性。同时收集患者的临床资料,包括组织学分型、病理学分级、Dukes分期、有无淋巴结转移等。结果ErbB-2在肠癌组织的基因表达(53.23±11.25)及蛋白表达(4183232.57±587378.18)比癌旁组织(38.21±6.20,2283766.18±376455.78)均明显增加(P<0.05),癌旁组织蛋白表达又高于远癌组织(1394280.24±6562.30)(P<0.05),但癌旁组织基因表达(38.21±6.20)与远癌组织(30.29±10.20)无显著差异。PAK1在肠癌组织基因(67.20±19.32)及蛋白表达(3879654.12±256332.02)较癌旁组织(26.50±7.22,1336987.25±98653.20)显著增加(P<0.01),远癌组织几乎未见表达。VEGF在肠癌组织的基因(62.30±33.58)及蛋白表达(4219314.65±433587.02)均高于癌旁组织(28.22±7.56,2275653.51±403731.20)及远癌组织(23.33±8.12,1878528.34±387563.71)(P<0.05)。三者在肠癌组织的表达呈现两两正相关关系,且与大肠癌的病理学分级、Dukes分期、淋巴结转移密切相关(P<0.05),而与组织学分型、肿瘤形态及发生部位无关。结论 ErbB-2、PAK1及VEGF在大肠癌发生发展中具有重要作用。ErbB-2活化后可激活下游分子PAK1及VEGF,后二者又相互促进表达,共同导致了大肠癌的演进侵袭。提示联合检测ErbB-2、PAK1及VEGF比单一检测判定大肠癌恶性行为及评估预后更有意义。

Objective To investigate the expression and correlation of ErbB-2,PAK1 and VEGF in colorectal carcinoma and their relationship with clinical pathological characters.Methods We selected 48 tissue specimens of colorectal carcinoma after radical resection,and divided them into 3groups:colorectal carcinoma tissues,pericancerous tissues and tissues distant from colorectal carcinoma.We adopted western blot and RT-PCR to detect the expression of proteins and genes of ErbB-2,PAK1 and VEGF,and analyzed their correlation.Results The expression of gene(53.23±11.25)and protein(4183232.57±587378.18)of ErbB-2in CRC was obviously more than in pericancerous tissues(38.21±6.20,2283766.18±376455.78)(P<0.05),and the protein expression was higher in pericancerous than indistant tissues(1394280.24±6562.30)(P<0.05),but there was no significant deviation in the gene expression between pericancerous and distant tissues.The expression of gene(67.20±19.32)and protein(3879654.12±256332.02)of PAK1 in CRC was significantly increased compared with that in pericancerous tissues(26.50±7.22,1336987.25±98653.20)(P<0.01),but there was nearly no expression indistant tissues.The expression of gene(62.30±33.58)and protein(4219314.65±433587.02)of VEGF in CRC was both higher than in pericancerous(28.22±7.56,2275653.51±403731.20)and distant tissues(23.33±8.12,1878528.34±387563.71)(P<0.05).In CRC,there were positive relations between ErbB-2,PAK1 and VEGF,and their expression was closely correlated to grading of CRC,Dukes deli-period and lymphatic metastasis.Conclusion ErbB-2,PAK1 and VEGFplay important roles during genesis and development of colorectal carcinoma.Activation of ErbB-2may activate downstreammolecules PAK1 and VEGF,and the latter two promote the expression of each other,thus inducing development and invasion of colorectal carcinoma.