乳腺癌组织中ING4、HIF-1α和HIF-2α表达及与肿瘤微血管新生的关系

摘要

Objective To investigate the expressions of ING4,HIF-1α and HIF-2α in breast cancer tissues and their relationship with tumor angiogenesis.Methods 107 cases of patients with breast cancer undergoing elective surgery were selected.Expressions of HIF-1α,HIF-2α,ING4 and VEGF genes in breast cancer and adjacent tissues were tested by real-time quantitative PCR.The microvessel density (MVD) in breast cancer and adjacent tissues were detected by using immunohistochemical staining.Results The relative expression levels of HIF-1α mRNA and HIF-2α mRNA in breast cancer tissues were higher than the adjacent tissues,while the relative expression levels of ING4 mRNA was lower than the adjacent tissues.The differences were statistically significant (P<0.05).The relative expression levels of HIF-1α mRNA were correlated with lymph node metastasis (P<0.05).The relative expression levels of HIF-2α mRNA were correlated with tumor size and lymph node metastasis (P<0.05),and the relative expression levels of ING4 mRNA were correlated with clinical stage and lymph node metastasis (P<0.05).The relative expression levels of VEGF mRNA and MVD counts in breast cancer tissues were significantly higher than those in adjacent tissues.The differences were statistically significant (P<0.05).Pearson correlation analysis showed that the relative expression levels of HIF-1α mRNA and HIF-2α mRNA were positively correlated with the relative levels of VEGF mRNA and MVD counts (r=0.382,0.417 and 0.408,0.491,P<0.05),and the expression levels of ING4 mRNA in breast cancer tissues were negatively correlated with the relative expression levels of VEGF mRNA and MVD counts (r=-0.395,-0.502,P<0.05).Conclusion The expressions of HIF-1α and HIF-2α genes in breast cancer tissues were up-regulated and ING4 gene was inhibited,which might be involved in the angiogenesis of breast cancer.%目的 探讨乳腺癌组织中生长抑制因子4(ING4)、缺氧诱导因子-1α(HIF-1α)和缺氧诱导因子-2α(HIF-2α)表达及与肿瘤微血管新生的关系.方法 选取择期行手术治疗的乳腺癌病人107例,利用实时荧光定量PCR技术检测乳腺癌和癌旁组织中HIF-1α、HIF-2α、ING4和血管内皮生长因子(VEGF)基因表达,免疫组化染色检测乳腺癌和癌旁组织中微血管密度(MVD).结果 乳腺癌组织中HIF-1α mRNA、HIF-2α mRNA相对表达量均高于癌旁组织,而ING4 mRNA 相对表达量低于癌旁组织,差异有统计学意义(P<0.05);HIF-1α mRNA相对表达量与淋巴结转移有关(P<0.05),HIF-2α mRNA相对表达量与肿瘤大小、淋巴结转移有关(P<0.05),ING4 mRNA相对表达量与临床分期、淋巴结转移有关(P<0.05);乳腺癌组织中VEGF mRNA相对表达量和MVD计数均高于癌旁组织,均差异有统计学意义(P<0.05);Pearson相关分析显示,乳腺癌组织中HIF-1α mRNA、HIF-2α mRNA相对表达量均与VEGF mRNA相对表达量和MVD计数呈正相关(r=0.382、0.417和0.408、0.491,P<0.05),ING4 mRNA相对表达量均与VEGF mRNA相对表达量和MVD计数呈负相关(r=-0.395、-0.502,P<0.05).结论 乳腺癌组织中HIF-1α、HIF-2α基因表达升高,而ING4基因则被抑制,可能共同参与了乳腺癌组织中血管新生.