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透明细胞肾细胞癌中 mA RNA 甲基转移酶的系统表达分析

Systematic expression analysis of mA RNA methyltransferases in clear cell renal cell carcinoma.

作者信息

Gundert Larissa, Strick Alexander, von Hagen Felix, Schmidt Doris, Klümper Niklas, Tolkach Yuri, Toma Marieta, Kristiansen Glen, Ritter Manuel, Ellinger Jörg

机构信息

Department of Urology University Hospital Bonn Bonn Germany.

Department of Pathology University Hospital Bonn Bonn Germany.

出版信息

BJUI Compass. 2021 May 3;2(6):402-411. doi: 10.1002/bco2.89. eCollection 2021 Nov.

DOI:10.1002/bco2.89
PMID:35474700
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8988738/
Abstract

OBJECTIVES

To investigate the regulation of the N-6-methyladenosine (mA) methyltransferases METTL3, METTL14, WTAP, KIAA1429, and METTL4, referred to as "mA writers," in clear cell renal cell carcinoma (ccRCC), and other RCC subtypes in respect of the potential prognostic value.

PATIENTS AND METHODS

Tissue samples were collected within the framework of the Biobank at the Center for Integrated Oncology Bonn. The expression of the methyltransferases was systematically determined in clear cell renal carcinoma (ccRCC) on the RNA (real-time PCR) and protein level (immunohistochemistry). Additionally, protein expression of the mA writers was further investigated in papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and normal renal tissue (immunohistochemistry).

RESULTS

The expression of all mA-methyltransferases was significantly downregulated in ccRCC compared to benign renal tissue. Low mA-methyltransferase levels were correlated with higher histological grade, advanced pT-stage, pN-stage, and metastatic disease. Reduced mA-methyltransferase expression was associated with shorter overall survival.

CONCLUSION

In conclusion, mA-methyltransferases are dysregulated in ccRCC and might act as tumor suppressor genes, which could be of particular importance for future diagnostic and therapeutic options.

摘要

目的

研究N-6-甲基腺苷（m⁶A）甲基转移酶METTL3、METTL14、WTAP、KIAA1429和METTL4（统称为“m⁶A书写蛋白”）在透明细胞肾细胞癌（ccRCC）及其他肾细胞癌亚型中的调控情况及其潜在的预后价值。

患者与方法

组织样本在波恩综合肿瘤中心生物样本库框架内收集。通过RNA（实时聚合酶链反应）和蛋白质水平（免疫组织化学）系统测定甲基转移酶在透明细胞肾细胞癌（ccRCC）中的表达。此外，通过免疫组织化学进一步研究m⁶A书写蛋白在乳头状肾细胞癌、嫌色细胞肾细胞癌、肉瘤样肾细胞癌、嗜酸细胞瘤和正常肾组织中的蛋白质表达。

结果

与良性肾组织相比，ccRCC中所有m⁶A甲基转移酶的表达均显著下调。低m⁶A甲基转移酶水平与更高的组织学分级、晚期pT分期、pN分期和转移性疾病相关。m⁶A甲基转移酶表达降低与总生存期缩短相关。

结论

总之，m⁶A甲基转移酶在ccRCC中表达失调，可能作为肿瘤抑制基因，这对未来的诊断和治疗选择可能具有特别重要的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2f8/8988738/65bf380ea00f/BCO2-2-402-g003.jpg
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