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。
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-1αand HIF-2αin both groups.Results The level of VHL in renal carcinoma group was significantly lower than that in control group,while levels of HIF-1αand HIF-2αwere significantly higher than those in control group(P<0.05).The level of VHL in renal carcinoma patients at stageⅠ/ⅡandⅢafter surgery was higher than that before surgery.VHL level in patients at stageⅠ/Ⅱwas higher than that at stageⅢ(P<0.05).The levels of HIF-1αand HIF-2αin renal carcinoma patients at stageⅠ/ⅡandⅢafter surgery were lower than those before surgery.And the above indexes in patients at stageⅠ/Ⅱwere lower than those at stageⅢ(P<0.05).The expression levels of serum VHL,HIF-1αand HIF-2αin 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-1αand HIF-2αwere 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-1αand HIF-1αwere 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-1αand HIF-2αwere positively correlated with it(P<0.05).The optimal cut-off values of serum VHL,HIF-1αand HIF-2αfor 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-1αand HIF-2αcan 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.
作者
王秋
林川
彭生才
陈洁
WANG Qiu;LIN Chuan;PENG Shengcai;CHEN Jie(Department of Oncology, Yibin Second People's Hospital, Yibin 644000, Sichuan, China)
出处
《西部医学》
2020年第7期1053-1057,共5页
Medical Journal of West China
基金
四川省科技计划项目(2016FZ0072)。
