AKT2在结肠癌中的表达及其临床意义
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摘要
目的检测丝氨酸/苏氨酸蛋白激酶2(AKT2)在结肠癌组织中以及正常结肠组织中的蛋白表达水平,探讨PI3K-AKT信号途径在结肠癌发生、发展中的作用,分析其与结肠癌临床病理资料间的关系。
方法本实验采用免疫组化SABC法以及免疫荧光法分别检测65例结肠癌手术切除标本的肿瘤组织和远癌切端结肠组织中AKT2蛋白的表达水平。将检测结果与相关临床指标进行统计学分析。
结果AKT2在结肠肿瘤组织中的阳性表达为69.23%,而在远癌切端结肠组织中表达为6.15%。结肠癌患者肿瘤组织中AKT2蛋白表达水平明显高于远癌切端结肠组织,两者间差异有统计学意义(P<0.05)。AKT2的表达与结肠癌Dukes分期、肿瘤侵润深度以及淋巴结转移有关(P<0.05),而与患者性别、年龄、分化程度及病理类型无相关性(P>0.05)。
结论AKT2在结肠癌的发生发展中发挥重要作用。AKT2通过PI3K/AKT信号途径调节多种下游靶基因、维持肿瘤细胞能量代谢、刺激新血管生成从而促进肿瘤细胞侵袭和转移,并能提高细胞的乏氧耐受,抵抗化疗药物对肿瘤细胞的影响,从而抑制其凋亡。AKT2在结肠癌组织中的异常表达对结肠癌的分期、转移及预后常有重要参考价值。AKT2有可能为结肠癌的基因治疗、抗结肠癌药物的开发提供新的作用靶点。
Objective To investigate the express of serine/threonine kinases 2 (AKT2) in colon carcinoma and normal colon tissue and the role of the PI3K/AKT signal pathway in the occurrence and development of colon carcinoma. To analyze its corre-lation with clinicopathological features of colon carcinoma.
Materials and Methods Immunohistochemistry(IHC) and immunofluorescence (IF) were used to determine the expressive levels of AKT2 protein in specimens of colon carcinoma and normal colon tissue in the surgical margin collected from 65 patients. Then the results and the clinical features were statistically analyzed.
Result The positive expression of AKT2 in colon cancer tissue is 69.23% while that of the surgical margin tissue is 6.15%.The AKT2 protein expression level in colon carcinoma was significantly higher than that of the surgical margin(P<0.05).There are correlations between AKT2 expressive level and colon carcinoma invasiveness, lymphathic metastasis, pathological grading as well as Dukes stage respectively(P<0.05),but no correlation was found between AKT2 expressive level and gender, age, tumor differentiation and histological type(P>0.05).
Conclusion AKT2 play an important role in the development of colon carcinoma.AKT2 can regulate its downstream target genes by the PI3K and AKT sig-naling pathway. The PI3K and AKT signaling pathway is crucial for tumor cell grow-th, angiogenesis, genome instability and tumor cell invasion and migration. Further-more, AKT2 can improve cell tolerance to hypoxia and was associated with chemore-sistance. The AKT2 protein over-expression in colon carcinoma play an important role in pathological grading, metastasis and prognosis. For this reason, AKT2 has become a viable drug target for colon carcinoma therapy and provided a new target for gene therapy.
方法本实验采用免疫组化SABC法以及免疫荧光法分别检测65例结肠癌手术切除标本的肿瘤组织和远癌切端结肠组织中AKT2蛋白的表达水平。将检测结果与相关临床指标进行统计学分析。
结果AKT2在结肠肿瘤组织中的阳性表达为69.23%,而在远癌切端结肠组织中表达为6.15%。结肠癌患者肿瘤组织中AKT2蛋白表达水平明显高于远癌切端结肠组织,两者间差异有统计学意义(P<0.05)。AKT2的表达与结肠癌Dukes分期、肿瘤侵润深度以及淋巴结转移有关(P<0.05),而与患者性别、年龄、分化程度及病理类型无相关性(P>0.05)。
结论AKT2在结肠癌的发生发展中发挥重要作用。AKT2通过PI3K/AKT信号途径调节多种下游靶基因、维持肿瘤细胞能量代谢、刺激新血管生成从而促进肿瘤细胞侵袭和转移,并能提高细胞的乏氧耐受,抵抗化疗药物对肿瘤细胞的影响,从而抑制其凋亡。AKT2在结肠癌组织中的异常表达对结肠癌的分期、转移及预后常有重要参考价值。AKT2有可能为结肠癌的基因治疗、抗结肠癌药物的开发提供新的作用靶点。
Objective To investigate the express of serine/threonine kinases 2 (AKT2) in colon carcinoma and normal colon tissue and the role of the PI3K/AKT signal pathway in the occurrence and development of colon carcinoma. To analyze its corre-lation with clinicopathological features of colon carcinoma.
Materials and Methods Immunohistochemistry(IHC) and immunofluorescence (IF) were used to determine the expressive levels of AKT2 protein in specimens of colon carcinoma and normal colon tissue in the surgical margin collected from 65 patients. Then the results and the clinical features were statistically analyzed.
Result The positive expression of AKT2 in colon cancer tissue is 69.23% while that of the surgical margin tissue is 6.15%.The AKT2 protein expression level in colon carcinoma was significantly higher than that of the surgical margin(P<0.05).There are correlations between AKT2 expressive level and colon carcinoma invasiveness, lymphathic metastasis, pathological grading as well as Dukes stage respectively(P<0.05),but no correlation was found between AKT2 expressive level and gender, age, tumor differentiation and histological type(P>0.05).
Conclusion AKT2 play an important role in the development of colon carcinoma.AKT2 can regulate its downstream target genes by the PI3K and AKT sig-naling pathway. The PI3K and AKT signaling pathway is crucial for tumor cell grow-th, angiogenesis, genome instability and tumor cell invasion and migration. Further-more, AKT2 can improve cell tolerance to hypoxia and was associated with chemore-sistance. The AKT2 protein over-expression in colon carcinoma play an important role in pathological grading, metastasis and prognosis. For this reason, AKT2 has become a viable drug target for colon carcinoma therapy and provided a new target for gene therapy.
引文
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[11]Xu X, Sakon M, Nagano H, et al.AKT2 expression correlates with prognosis of human hepatocellular carcinoma[J].Oncol Rep,2004,11(1);25—32.
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