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N6-甲基腺苷(m A)去甲基酶烷基化修复同源物 5(ALKBH5)和肥胖相关蛋白(FTO)是透明细胞肾细胞癌患者的预后生物标志物。

The N -methyladenosine (m A) erasers alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) are prognostic biomarkers in patients with clear cell renal carcinoma.

机构信息

Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany.

Institut für Pathologie, Universitätsklinikum Bonn, Bonn, Germany.

出版信息

BJU Int. 2020 Apr;125(4):617-624. doi: 10.1111/bju.15019. Epub 2020 Feb 17.

Abstract

OBJECTIVES

To comprehensively investigate the role of the N -methyladenosine (m A) erasers ALKBH5 and FTO in clear cell renal cell carcinoma (ccRCC), other RCC subtypes, and oncocytoma with respect to prognostic value and biomarker potential.

PATIENTS AND METHODS

The collection of tissue samples was performed within the framework of the Biobank at the Centre for Integrated Oncology Cologne-Bonn. The gene expressions of alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) were determined using quantitative real-time polymerase chain reaction. ALKBH5 and FTO expressions were further investigated in ccRCC, papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and benign renal tissue using tissue microarrays.

RESULTS

ALKBH5 mRNA, as well as ALKBH5 and FTO protein expressions, was significantly downregulated in ccRCC compared to normal tissue and most of the other studied tumour entities. Decreased mRNA levels of ALKBH5 and FTO correlated with a shortened overall and cancer-specific survival following nephrectomy.

CONCLUSIONS

Taken together, our present data indicate that the m A-demethylases ALKBH5 and FTO are dysregulated in ccRCC and could be used as prognostic biomarkers.

摘要

目的

全面研究 N6-甲基腺苷(m6A)去甲基酶 ALKBH5 和 FTO 在透明细胞肾细胞癌(ccRCC)、其他 RCC 亚型和嗜酸细胞瘤中的作用,包括其预后价值和生物标志物潜力。

方法

组织样本的采集是在科隆波恩综合肿瘤学中心的生物库框架内进行的。采用实时定量聚合酶链反应测定烷基化修复同源物 5(ALKBH5)和脂肪量和肥胖相关蛋白(FTO)的基因表达。使用组织微阵列进一步研究 ccRCC、乳头状 RCC、嫌色细胞 RCC、肉瘤样 RCC、嗜酸细胞瘤和良性肾组织中的 ALKBH5 和 FTO 表达。

结果

与正常组织和大多数其他研究的肿瘤实体相比,ccRCC 中 ALKBH5 mRNA 以及 ALKBH5 和 FTO 蛋白的表达均显著下调。ALKBH5 和 FTO 的 mRNA 水平降低与肾切除术后总生存期和癌症特异性生存期缩短相关。

结论

综上所述,我们目前的数据表明,m6A 去甲基酶 ALKBH5 和 FTO 在 ccRCC 中失调,可作为预后生物标志物。

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