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肾癌患者血清VHL和HIF-1α与HIF-2α的表达及其与预后的相关性
王秋,林川,彭生才,陈洁
0
(宜宾市第二人民医院肿瘤科)
摘要:
【摘要】目的 探讨肾癌患者血清希佩尔林道基因(VHL)、缺氧诱导因子1(HIF1α)和缺氧诱导因子2(HIF2α)的表达及与预后的相关性分析。 方法 选取2015年3月~2016年3月我院收治的82例肾癌患者为肾癌组,同时选取51例健康者为对照组。利用酶联免疫吸附法(ELISA)测定两组的VHL、HIF1α及HIF2α水平。结果 肾癌组患者VHL水平比对照组明显降低,HIF1α、HIF2α水平比对照组明显升高(P<005);Ⅰ/Ⅱ、Ⅲ期肾癌患者术后VHL水平均高于术前,且Ⅰ/Ⅱ期高于Ⅲ期(P<005);Ⅰ/Ⅱ、Ⅲ期肾癌患者术后HIF1α、HIF2α水平均低于术前,且Ⅰ/Ⅱ期低于Ⅲ期(P<005);肾癌患者血清VHL、HIF1α及HIF2α表达水平与年龄、性别无关(均P>005),与病灶直径、淋巴结转移、病理分级、TNM分期相关(均P<005);肾癌患者3年生存率与患者年龄、性别无关(均P>005),患者VHL高表达的3年生存率明显高于VHL低表达(P<005),患者HIF1α、HIF2α高表达的3年生存率明显低于HIF1α、HIF2α低表达(均P<005);血清VHL低表达、血清HIF1α、HIF1α高表达是肾癌患者术后肾衰竭的独立危险因素;患者VHL水平与发生肾癌呈负相关,HIF1α、HIF2α水平与发生肾癌呈正相关(P<005);血清VHL、HIF1α、HIF2α预测肾癌患者的最佳截值分别为37978、771、095,三者联合预测的AUC大于VHL(Z=8268,P<005),HIF1α(Z=8268,P<005),HIF2α(Z=8268,P<005)。结论 血清VHL、HIF1α和HIF2α对肾癌患者具有较好的预后预测价值,可作为肾癌患者发生、发展的重要指标及预后预测的分子标志物,三者联合应用能提高其预后预测能力。
关键词:  肾癌  希佩尔 林道基因  缺氧诱导因子 1  缺氧诱导因子 2  病理分级  远期生存率
DOI:
基金项目:四川省科技计划项目(2016FZ0072)
Expression of serum VHL, HIF-1α and HIF 2α in renal carcinoma patients and their correlation with prognosis
WANG Qiu,LIN Chuan,PENG Shengcai,CHEN Jie
(Department of Oncology, Yibin Second People's Hospital)
Abstract:
【Abstract】Objective To explore expression of serum Von HippelLindau (VHL), hypoxiainducible factor1 (HIF1α) and hypoxiainducible factor2 (HIF2α) in renal carcinoma patients and their correlation with prognosis. Methods Eightytwo patients with renal carcinoma admitted to the hospital from March 2015 to March 2016 were enrolled as renal carcinoma group. 51 healthy people were enrolled as control group. The enzymelinked immunosorbent assay (ELISA) was performed to determine levels of VHL, HIF1α and HIF2α in both groups. Results The level of VHL in renal carcinoma group was significantly lower than that in control group, while levels of HIF1α and HIF2α were significantly higher than those in control group (P<005). The level of VHL in renal carcinoma patients at stage Ⅰ/Ⅱ and Ⅲ after surgery was higher than that before surgery. VHL level in patients at stage Ⅰ/Ⅱ was higher than that at stage Ⅲ (P<005). The levels of HIF1α and HIF2α in renal carcinoma patients at stage Ⅰ/Ⅱ and Ⅲ after surgery were lower than those before surgery. And the above indexes in patients at stage Ⅰ/Ⅱ were lower than those at stage Ⅲ (P<005). The expression levels of serum VHL, HIF1α and HIF2α in renal carcinoma patients were not related with age or gender (P>005), while related with lesion diameter, lymph node metastasis, pathological grading and TNM staging (P<005). The 3year survival rate of renal cancer carcinoma was not related with age or gender (P>005). The 3year survival rate of patients with VHL high expression was significantly higher than that with VHL low expression (8333% vs 6000%) (P<005), while 3year survival rates of patients with high expression of HIF1α and HIF2α were significantly lower than those with low expression of HIF1α, HIF2α (5098%, 5217% vs 7742%, 8055%) (P<005). The low expression of serum VHL, high expression of serum HIF1α and HIF1α were independent risk factors of postoperative kidney failure in renal carcinoma patients. The level of VHL was negatively correlated with occurrence of renal carcinoma, while HIF1α and HIF2α were positively correlated with it (P<005). The optimal cutoff values of serum VHL, HIF1α and HIF2α for predicting renal carcinoma patients were 37978, 771 and 095, respectively. AUC of combination prediction of the three was greater than that of VHL (Z=8268, P<005), HIF1α (Z=8268, P<005) and HIF2α (Z=8268, P<005). Conclusion Serum VHL, HIF1α and HIF2α can be applied as important indexes to determine occurrence and development of renal carcinoma. They can not only affect shortterm survival rate of patients, but also are of good prediction value for prognosis of renal carcinoma patients. They can be applied as molecular markers of prognosis prediction. The combination application of the three can improve prediction ability of prognosis.
Key words:  Renal carcinoma  Von Hippel Lindau  Hypoxia inducible factor 1  Hypoxia inducible factor 2  Pathological grade  Long term survival

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