机体乏氧与肾癌肿瘤微血管生成及预后的关系

Relationship between Condition of Hypoxia and Tumor Angiogenesis and Prognosis in Patients with Renal Carcinoma

【目的】探讨机体乏氧状态下肾透明细胞癌患者肿瘤微血管生成、术后生存期同一般患者的差异,借以评价机体乏氧在肾癌预后中的地位及作用机制。【方法】56例肾透明细胞癌行根治性肾切除手术患者,分为机体乏氧状态组(OH组,14例)和机体常氧状态组(NS组,42例),免疫组化检测手术标本中缺氧诱导因子-1ɑ(HIF-1ɑ)表达,测量CD105标志的肿瘤微血管密度(MVD),随访术后生存时间,对比二组临床病理资料差别,Kaplan-Meier法分析二组生存率,建立COX模型分析各变量与生存时间的相关性。【结果】OH组表达HIF-1ɑ的阳性率为92.9%(13/14),MVD值为53.1±19.9,中位生存时间为(42.0±10.2)月,NS组表达HIF-1ɑ的阳性率为64.3%(27/42),MVD值为42.8±14.4,中位生存时间为(84.0±6.1)月,二组Hb水平、HIF-1ɑ表达、MVD值间差异有统计学意义。COX分析提示肿瘤高分期、机体乏氧状态、肿瘤HIF-1ɑ高表达和MVD值高可以增加患者的死亡风险(RR依次为2.0、4.1、1.1和4.0)。【结论】机体乏氧状态可加剧肿瘤内部的缺氧,上调HIF-1ɑ表达,促进肿瘤微血管形成,最终恶化肾透明细胞癌患者的预后。

[Objective]To explore the difference of tumor angiogenesis and postoperative survival between condition of hypoxia patients and general patients with renal clear cell carcinoma , and assess the status and mechanisms of condition of hypoxia in the patients with the renal clear cell carcinoma. [Methods] Fifty-six cases of renal clear cell carcinoma with radical nephrectomy surgery were divided into condition of hypoxia group （OH group, 14 cases） and condition of normoxia group （NS group, 42 cases）. Immunohistochemieal detection of hypoxia inducible factor-la （HIF-lu） of surgical specimens and measure of microvessel density （MVD） with CD105 flag. To follow up survival time and contrast the difference of clinical and pathological data in two groups, and the survival rate in two groups was evaluated by Kaplan-Meier method. And the COX model was build to analyze the correlation between each variable and survival time. [Results] In OH group, the positive expression rate of HIF-1a was 92.9% （13/14） and the MVD value was 53.1 ±19.9, median survival time was 42.0±10.2 months. In NS group, the positive expression rate of HIF-1a was 64.3% （27/42）, and the MVD value was 42.8±14.4, median survival time was 84.0±6.1 months. In two groups, Hb level, HIF- 1a expression, MVD value were significantly different. COX multivariate analysis showed that high stage, organism hypoxia, high expression of HIF-1a and high MVD in tumor can increase the risk of death （RR followed were 2.0, 4.1, 1.1, and 4.0）. [Conclusion] Condition of hypoxia may exacerbate hypoxia within the tumor, increasing HIF- 1a expression, and promote tumor angiogenesis, eventually worsen the prognosis in the patient with renal clear cell carcinoma.