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缺氧诱导因子-1α和趋化因子受体4在食管鳞癌中的表达及其临床意义

Expression and clinical significance of hypoxia inducible factor-1 a and chemokine receptor 4 in esophageal squamous carcinoma

摘要:

目的 观察缺氧对食管癌细胞株Caes-17中缺氧诱导因子-1 α(HIF-1α)和趋化因子受体4(CXCR4)表达的影响以及两者在食管鳞癌组织中表达意义及相关性.方法 体外培养人食管癌Caes-17细胞株,应用实时定量聚合酶链反应(Real-time PCR)和Western blot检测常氧和缺氧条件下Caes-17中HIF-1α和CXCR4的表达;应用免疫组织化学链菌素抗生物素蛋白-过氧化物酶(SP)法检测106例有完整临床病理资料的食管鳞癌(ESCC)和30例正常食管黏膜组织中HIF-1α和CXCR4蛋白的表达,分析HIF-1α和CXCR4的表达与患者临床病理特征的关系及两者之间的相关性.结果 缺氧条件下,HIF-1 α蛋白(0.86 ±0.03)、CXCR4 mRNA (6.95±0.30)、CXCR4蛋白(0.56 ±0.02)表达与常氧下HIF-1α蛋白(0.28±0.04)、CXCR4 mRNA(1.09±0.14)、CXCR4蛋白(0.11±0.03)表达比较均显著升高(P<0.05),缺氧时HIF-1αmRNA(0.96±0.06)与常氧条件下(1.14±0.12)比较差异无统计学意义(P >0.05);HIF-1α和CXCR4在食管鳞癌组织中的阳性表达率均明显高于正常食管黏膜组织(P<0.05),HIF-1α表达与食管鳞癌的浸润深度、淋巴结转移及TNM分期密切相关(P<0.05),CXCR4表达与肿瘤浸润深度、淋巴结转移密切相关(P<0.05),HIF-1α与CXCR4的表达呈正相关(r=0.539,P<0.05).结论 缺氧可诱导HIF-1 α和CXCR4在食管癌细胞中的表达;HIF-1α和CXCR4在食管鳞癌组织中表达密切相关,有可能在食管鳞癌的发生发展和侵袭转移中起协同作用.

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abstracts:

Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) and chemokine receptor 4 (CXCR4) in Caes-17 cells under hypoxia,and investigate the expression and clinical significance of HIF-1 α and CXCR4 in esophageal squamous cell carcinoma (ESCC) tissues and their correlation.Methods Caes-17 cells were cultured in vitro.The expression of HIF-1α and CXCR4 was detected by using fluorescence real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting under normoxia or hypoxia.The expressions of HIF-1α and CXCR4 protein was assessed by using immunohistochemistry in 106 cases of ESCC specimens with complete clinical and pathological date and 30 cases of normal esophageal mucosa tissues.The relationship between HIF-1 α or CXCR4 and pathologic features of esophageal cancer was analyzed.The correlation between HIF-1α and CXCR4 was also assessed.Results The expression of HIF-1α protein (0.86 ±0.03),CXCR4 mRNA (6.95 ±0.30),CXCR4 protein (0.56 ± 0.02) were increased under hypoxia than those under normoxia [HIF-1 α protein (0.28±0.04),CXCR4 mRNA (1.09±0.14),CXCR4 protein (0.11±0.03)] (P<0.05).There was no significant difference in HIF-1 α mRNA (0.96 ± 0.06) between hypoxia and normoxia (1.14 ± 0.12) (P > 0.05).The positive rate of HIF-1α and CXCR4 expression in ESCC tissues was obviously higher than that in normal esophageal mucosa tissues (P < 0.05).The expression of HIF-1 α in ESCC tissues was associated with depth of tumor invasion,lymph node metastasis and TNM stage (P < 0.05) and the expression of CXCR4 in ESCC tissues was associated with depth of tumor invasion,lymph node metastasis (P < 0.05).The expression of CXCR4 was significantly correlated with the expression of HIF-1α(r =0.539,P < 0.05).Conclusion Hypoxia can increase the expression level of HIF-1 α and CXCR4 in esophageal cancer cells.The CXCR4 expression has a significantly positive correlation with the HIF-1α expression in esophageal cancer.They may play synergetic roles in the genesis,development,invasion and metastasis of ESCC.

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