Hypoxia-inducible factor-2α mRNA expression in human renal cell carcinoma
Hypoxia-inducible factor-2α mRNA expression in human renal cell carcinoma
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DOI：
10.1080/02841860902824891
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发表时间：
2009-01-01
期刊：
影响因子：
3.1
通讯作者：
Rasmuson, Torgny
中科院分区：
文献类型：
--
作者：
Sandlund, Johanna;Ljungberg, Borje;Rasmuson, Torgny
背景资料。低氧诱导因子-2α在低氧或von Hippel-Lindau(VHL)肿瘤抑制基因失活时上调。在许多恶性肿瘤中，HIF-2α的高表达可能预示着较差的预后。本研究旨在探讨低氧诱导因子-2α(HIF-2α)在肾细胞癌(RCC)中的表达及其与预后的关系。材料和方法。采用实时定量聚合酶链式反应(RT-PCR)检测202例肿瘤组织标本中HIF-2αmRNA的表达。以50例相应肾皮质组织标本为对照进行分析。评估mRNA水平与肿瘤细胞类型、TNM分期、核分级和疾病特异性生存的关系。结果。透明细胞肾癌HIF-2α的表达水平显著高于23例乳头状肾癌(p<；0.001)和11例嫌色肾细胞癌(p<；0.006)。在肾细胞癌中，HIF-2α基因表达水平与肿瘤的临床分期呈负相关(P=0.006)，与肿瘤的分期呈负相关(P=0.05)。中位随访时间99个月(范围34-247)，106名患者死于肾癌。未观察到HIF-2αmRNA与存活期的相关性。对CRCC预后因素的多因素分析显示，单独的TNM分期是预后的独立预测因素；HIF-2αmRNA水平不能增加进一步的预后信息。讨论。结果表明，CRCC组织中HIF-2α的表达水平高于pRCC和CHRCC。此外，HIF-2αmRNA表达水平与肾细胞癌的TNM分期和核分级呈负相关。
Background. Hypoxia-inducible factor (HIF)-2 alpha is upregulated in hypoxia or by inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. In a number of malignancies, increased HIF-2 alpha expression may indicate worse prognosis. The aim of this study was to evaluate the prognostic information of HIF-2 alpha mRNA expression in renal cell carcinoma (RCC). Material and methods. HIF-2 alpha mRNA was quantified by real time polymerase chain reaction (rt-PCR) in tumour tissue samples from 202 patients. Samples from 50 corresponding kidney cortex tissue were analysed as controls. mRNA levels were evaluated in relation to tumour cell type, TNM stage, nuclear grade and disease specific survival. Results. The levels of HIF-2 alpha mRNA were significantly higher in 168 clear cell (c) RCC than in 23 papillary (p) RCC (p < 0.001) or 11 chromophobe (ch) RCC (p < 0.006). Among cRCC there was an inverse correlation between HIF-2 alpha mRNA levels and TNM stage I and II-IV tumours (p = 0.01), and nuclear grade (p = 0.006). After a median follow-up time of 99 months (range 34-247), 106 patients had died of RCC. No correlation of HIF-2 alpha mRNA to survival was observed. A multivariate analysis of prognostic factors in cRCC showed that TNM stage alone was an independent predictor of prognosis; HIF-2 alpha mRNA levels did not add further prognostic information. Discussion. The results demonstrated that HIF-2 alpha mRNA levels were higher in cRCC compared to pRCC and chRCC. Furthermore, HIF-2 alpha mRNA levels were inversely related to TNM stage and nuclear grade in cRCC.