活化CDC42相关激酶1表达与食管鳞状细胞癌侵袭转移的相关性研究
Correlation between expression of ACK1 and invasion and metastasis of esophageal squamous cell ;carcinoma
摘要目的:探讨活化CDC42相关激酶1(ACK1)表达与食管鳞状细胞癌侵袭转移的相关性。方法采用RT?PCR技术、免疫组化检测了45例新鲜深低温保存的食管鳞癌组织及癌旁正常粘膜组织样本中ACK1 mRNA、ACK1蛋白表达情况;分析5株食管鳞癌细胞系中ACK1的表达状况,可使用Western印迹进行检测。分析ACK1在mRNA水平和蛋白水平差异表达与食管鳞癌各临床病理特征之间的关系。结果 ACK1 mRNA和蛋白在食管癌旁正常粘膜组织中仅有较低水平的表达,而在食管鳞癌组织中,ACK1 mRNA在60%(27/45)的食管鳞癌组织中表达上调,ACK1蛋白在64.4%(29/45)食管鳞癌组织中表达上调,而且这种表达变化具有良好的一致性(P=0.02)。统计学分析显示ACK1 mRNA和蛋白的高表达均与病人的淋巴结转移、肿瘤分期相关(P<0.05)。免疫组化结果显示ACK1在大多数食管鳞癌细胞的胞浆中表达上调,在癌巢周边外侵的肿瘤细胞中ACK1蛋白表达更为丰富,这个现象也表明ACK1高表达与肿瘤细胞侵袭能力正相关。结论 ACK1高表达与食管鳞癌的恶性表型和不良预后呈正相关。通过检测ACK1也许可以预期食管鳞癌侵袭和淋巴结转移发生的概率,判断肿瘤预后转归,为肿瘤个体化治疗提供依据。
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abstractsObjective To investigate the correlation between the expression of activated CDC42?associated tyrosine kinase 1(ACK1)and invasion and metastasis of esophageal squamous cell carcinoma (ESCC). Methods RT?PCR technique and immunohistochemical(IHC)assay were used to determine the expression levels of ACK1 mRNA and protein in 45 cases of freezing stored fresh ESCC tissues and ESCC?adjacent normal mucosa tissues. Western blotting was used to determine the expression of ACK1 in 5 ESCC cell lines. The correlation between the different expression levels of ACK1 mRNA and protein and ESCC clinical and pathological features was analyzed. Results Low expression of ACK1 mRNA and protein was found in ESCC?adjacent normal mucosa tissues. In ESCC tissues,the expression levels of ACK1 mRNA and protein were up?regulated in 60%(27/45) and 64.4%(29/45) ESCC tissues,respectively,with good consistency(P=0.02). Statistical analysis showed high expression of ACK1 mRNA and protein,which were significantly correlated with the metastasis of lymph node and tumor staging (P<0.05). Immunohistochemistry showed up?regulated expression of ACK1 in most ESCC cytoplasm,and high expression of ACK1 protein in ESCC nest surrounding invaded tumor cells,indicating positive correlation between ACK1 high expression and tumor cell invasiveness. Conclusion ACK1 high expression is positively correlated with malignant phenotype and poor prognosis of ESCC. Measuring the expression level of ACK1 may predict the ratio of tumor invasion,lymphonode metastasis,and prognosis in ESCC,to provide evidence for individualized cancer therapy.
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