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

Expressions of ING4,HIF-1α and HIF-2α in breast cancer tissues and their relationship with tumor angiogenesis

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-1αmRNA、HIF-2αmRNA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-1αmRNA相对表达量与淋巴结转移有关(P<0.05),HIF-2αmRNA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-1αmRNA、HIF-2αmRNA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。

Objective To investigate the expressions of ING4,HIF-la and HIF-2a 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- 1 a, HIF-2a, 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 ex-pression levels of HIF-la mRNA and HIF-2a 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 rela-tive expression levels of HIF-la mRNA were correlated with lymph node metastasis （ P 〈0. 0 5 ） . The relative expression levels of HIF- 2a mRNA were correlated with tumor size and lymph node metastasis （ P 〈 0 .0 5 ） ,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-la mRNA and HIF-2a mRNA were positively cor-related 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 H IF - la and HIF-2a genes in breast cancer tissues were up-regulated and ING4 gene was inhibited, which might be involved in the angiogenesis of breast cancer.