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卵巢浆液性癌中AlkB家族的表达及分子特征

Expression and molecular profiles of the AlkB family in ovarian serous carcinoma.

作者信息

Cai Yuan, Wu Geting, Peng Bi, Li Juanni, Zeng Shuangshuang, Yan Yuanliang, Xu Zhijie

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

出版信息

Aging (Albany NY). 2021 Mar 19;13(7):9679-9692. doi: 10.18632/aging.202716.

DOI:10.18632/aging.202716
PMID:33744868
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8064172/
Abstract

AlkB family of Fe (II) and α-ketoglutarate-dependent dioxygenases plays essential roles in development of ovarian serous carcinoma (OV). However, the molecular profiles of AlkB family in OV have not been clarified. The results indicated that the expression of ALKBH1/3/5/8 and FTO was lower in OV patients while ALKBH2/4/6/7 expression was higher. There was a strong correlation between ALKBH5/7 and pathological stage of OV patients. Kaplan-Meier plotter revealed that OV patients with high ALKBH4 level showed longer overall survival (OS). However, patients with high levels of ALKBH5/6 and FTO showed shorter OS and progression-free survival (PFS). Genetic alterations using cBioPortal revealed that the alteration rates of FTO were the highest. We also found that the functions of AlkB family were linked to several cancer-associated signaling pathways, including chemokine receptor signaling. TIMER database indicated that the AlkB family had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, DiseaseMeth databases revealed that the global methylation levels of ALKBH1/2/3/4/5/6/7/8 and FTO were all lower in OV patients. Thus, our findings will enhance the understanding of AlkB family in OV pathology, and provide novel insights into AlkB-targeted therapy for OV patients.

摘要

铁（II）和α-酮戊二酸依赖性双加氧酶的AlkB家族在卵巢浆液性癌（OV）的发展中起重要作用。然而，AlkB家族在OV中的分子特征尚未阐明。结果表明，OV患者中ALKBH1/3/5/8和FTO的表达较低，而ALKBH2/4/6/7的表达较高。ALKBH5/7与OV患者的病理分期之间存在很强的相关性。Kaplan-Meier绘图仪显示，ALKBH4水平高的OV患者总生存期（OS）更长。然而，ALKBH5/6和FTO水平高的患者OS和无进展生存期（PFS）较短。使用cBioPortal进行的基因改变分析显示，FTO的改变率最高。我们还发现AlkB家族的功能与几种癌症相关信号通路有关，包括趋化因子受体信号通路。TIMER数据库表明，AlkB家族与六种免疫细胞（巨噬细胞、中性粒细胞、CD8 + T细胞、B细胞、CD4 + T细胞和树突状细胞）的浸润有很强的关系。接下来，DiseaseMeth数据库显示，OV患者中ALKBH1/2/3/4/5/6/7/8和FTO的整体甲基化水平均较低。因此，我们的研究结果将增进对AlkB家族在OV病理学中的理解，并为OV患者的AlkB靶向治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/cc9a50329abb/aging-13-202716-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/46e4e1424b02/aging-13-202716-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/b4ebb1dc4fab/aging-13-202716-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/efd1bf368b68/aging-13-202716-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/5f0f9f40dcee/aging-13-202716-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/6e3068c797b6/aging-13-202716-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/c6a16ef1bf9c/aging-13-202716-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/e7a3ffe517b0/aging-13-202716-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/bbbbb14ad057/aging-13-202716-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/cc9a50329abb/aging-13-202716-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/46e4e1424b02/aging-13-202716-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/b4ebb1dc4fab/aging-13-202716-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/efd1bf368b68/aging-13-202716-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/5f0f9f40dcee/aging-13-202716-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/6e3068c797b6/aging-13-202716-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/c6a16ef1bf9c/aging-13-202716-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/e7a3ffe517b0/aging-13-202716-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/bbbbb14ad057/aging-13-202716-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0cd/8064172/cc9a50329abb/aging-13-202716-g009.jpg

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