缺氧诱导因子-2α 在人肾细胞癌中的 mRNA 表达。

Hypoxia-inducible factor-2alpha mRNA expression in human renal cell carcinoma.

机构信息

Department of Radiation Sciences, Oncology, Umeå University, Sweden.

出版信息

Acta Oncol. 2009;48(6):909-14. doi: 10.1080/02841860902824891.

DOI:10.1080/02841860902824891

PMID:19322701

Abstract

BACKGROUND

Hypoxia-inducible factor (HIF)-2alpha is upregulated in hypoxia or by inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. In a number of malignancies, increased HIF-2alpha expression may indicate worse prognosis. The aim of this study was to evaluate the prognostic information of HIF-2alpha mRNA expression in renal cell carcinoma (RCC).

MATERIAL AND METHODS

HIF-2alpha 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-2alpha 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-2alpha 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-2alpha 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-2alpha mRNA levels did not add further prognostic information.

DISCUSSION

The results demonstrated that HIF-2alpha mRNA levels were higher in cRCC compared to pRCC and chRCC. Furthermore, HIF-2alpha mRNA levels were inversely related to TNM stage and nuclear grade in cRCC.

摘要

背景

缺氧诱导因子（HIF）-2α在缺氧或抑癌基因 von Hippel-Lindau（VHL）失活的情况下会被上调。在许多恶性肿瘤中，HIF-2α表达增加可能预示着预后较差。本研究旨在评估肾细胞癌（RCC）中 HIF-2αmRNA 表达的预后信息。

材料与方法

通过实时聚合酶链反应（rt-PCR）在 202 例患者的肿瘤组织样本中定量 HIF-2αmRNA。分析了 50 个相应的肾皮质组织样本作为对照。评估了 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

168 例透明细胞（c）RCC 的 HIF-2αmRNA 水平明显高于 23 例乳头状（p）RCC（p<0.001）或 11 例嫌色细胞（ch）RCC（p<0.006）。在 cRCC 中，HIF-2αmRNA 水平与 TNM 分期 I 期和 II-IV 期肿瘤（p=0.01）以及核分级（p=0.006）呈负相关。中位随访时间为 99 个月（范围 34-247）后，106 例患者死于 RCC。未观察到 HIF-2αmRNA 与生存相关。cRCC 中预后因素的多变量分析表明，TNM 分期是独立的预后预测因素；HIF-2αmRNA 水平未提供额外的预后信息。