实验发现,HIF-1α在正常肾组织无阳性表达,而在54例肾癌组织中阳性表达率55.6%,提示多数肾癌组织缺氧导致HIF-1α过表达,激活多种靶基因的转录,使之适应缺氧环境。
CAⅨ 是由酸性氨基酸组成的跨膜糖蛋白,CAⅨ 能够催化CO2水化生成H+和HCO-3,HCO-3与细胞内Cl-交换,维持细胞内碱性环境,有利于细胞的生长;细胞内H+则通过离子泵、H+-Na+交换等方式运输到细胞外,使细胞外为酸性微环境,细胞外酸性环境可以激活细胞表面蛋白,在调控细胞增殖、转化方面有重要作用,并有利于肿瘤的生长和转移[6]。CAⅨ 位于VHL肿瘤抑制基因的下游,由HIF-1途径激活,在正常组织中表达极低,在肾细胞癌中高度表达。本实验显示,CAⅨ 肾癌表达率为68.5%(37/54),与肿瘤的病理细胞类型、病理分级、临床分期无明显相关性。
本组结果显示,HIF-1α与CAⅨ在肾癌组织中表达呈正相关关系(r=0.437,P=0.001)。HIF-1α与CAⅨ 在正常组织中表达极低,在肾细胞癌中高表达,且肾癌对放化疗不敏感,免疫治疗有效率<30%[7],提示HIF-1α与CAⅨ 可能成为判断肾癌转移与预后等生物学行为的重要参考指标并成为抗肿瘤治疗的新靶点。通过针对HIF-1α的治疗,抑制下游靶基因的表达,直接影响肿瘤的能量代谢及血管生成,有望取得满意的临床疗效。
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