Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas
Nuclear karyopherin a2: a novel biomarker for infiltrative astrocytomas
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DOI：
10.1007/s11060-012-0924-2
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发表时间：
2012-09-01
影响因子：
3.9
通讯作者：
Niehusmann, P.
中科院分区：
文献类型：
--
作者：
Gousias, K.;Becker, A. J.;Niehusmann, P.
核浆转运蛋白（KPNA）蛋白家族参与核质运输。已发现增加的KPNA水平预测多种实体瘤的不良预后，包括乳腺癌、卵巢癌、宫颈癌和前列腺癌以及黑色素瘤。本研究的目的是评价核转运蛋白a2作为WHO II-IV级星形胶质细胞瘤的新生物标志物。我们通过免疫组化分析半定量测定了94例原发性（23例星形细胞瘤WHO II级，24例星形细胞瘤WHO III级，47例胶质母细胞瘤）和12例复发性胶质瘤的核内嗜核蛋白a2表达和MIB 1标记指数。此外，IDH 1突变状态和奈梅亨断裂综合征1蛋白表达进行了评估，免疫组化分析，分别为所有71恶性（WHO III级和IV级）和所有94原发性胶质瘤。使用标准技术进行统计分析。Karyopherin α 2表达与组织学分级（p < 0.001）、增殖活性（如MIB 1指数评估的）（p < 0.001）、IDH 1突变状态（p = 0.032）和Nijmegen断裂综合征1蛋白表达（p = 0.001）显著相关。复发性肿瘤表达的karyopherin a2水平显著高于原发性肿瘤（p = 0.045）。对整个系列的多变量分析表明，低核转运蛋白a2表达（定义为低于5%）是总体（p = 0.041）和无进展生存期（p = 0.004）的独立预后预测因子。胶质母细胞瘤患者的生存期> 5年仅见于KPNA 2表达水平为千分之一货币符号的患者1%（p = 0.014）。KPNA 2表达可能成为星形胶质细胞瘤诊断和预后的新生物标志物。
The karyopherin (KPNA) protein family is involved in nucleocytoplasmic trafficking. Increased KPNA levels have been found to predict poor prognosis for a variety of solid tumors, including breast, ovarian, cervical, and prostate cancer, and melanoma. The purpose of this study was to evaluate karyopherin a2 as novel biomarker for astrocytic gliomas of WHO grades II-IV. We semiquantitatively measured nuclear expression of karyopherin a2 and the MIB1 labeling index, by immunohistochemical analysis, for 94 primary (23 astrocytomas WHO grade II, 24 astrocytomas WHO grade III, 47 glioblastomas) and 12 recurrent gliomas. In addition, IDH1 mutation status and Nijmegen breakage syndrome 1 protein expression were assessed, by immunohistochemical analysis, for all 71 malignant (WHO grade III and IV) and all 94 primary gliomas, respectively. Statistical analysis was performed by use of standard techniques. Karyopherin a2 expression correlated significantly with histological grade (p < 0.001), with proliferative activity as assessed by the MIB1 index (p < 0.001), with IDH1 mutation status (p = 0.032), and with Nijmegen breakage syndrome 1 protein expression (p = 0.001). Recurrent tumors expressed significantly higher levels of karyopherin a2 (p = 0.045) than primary growths. Multivariate analysis of the overall series identified low karyopherin a2 expression (defined as less than 5 %) as an independent prognostic predictor of overall (p = 0.041) and progression-free survival (p = 0.004). Survival of glioblastoma patients > 5 years was seen only in those with KPNA2 expression levels a parts per thousand currency sign1 % (p = 0.014). KPNA2 expression may have potential as a novel diagnostic and prognostic biomarker for astrocytic gliomas.