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日本女性原发性乳腺癌中载脂蛋白B mRNA编辑酶催化多肽样3B(APOBEC3B)的表达

Expression of APOBEC3B mRNA in Primary Breast Cancer of Japanese Women.

作者信息

Tokunaga Eriko, Yamashita Nami, Tanaka Kimihiro, Inoue Yuka, Akiyoshi Sayuri, Saeki Hiroshi, Oki Eiji, Kitao Hiroyuki, Maehara Yoshihiko

机构信息

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan.

Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka, Japan.

出版信息

PLoS One. 2016 Dec 15;11(12):e0168090. doi: 10.1371/journal.pone.0168090. eCollection 2016.

DOI:10.1371/journal.pone.0168090
PMID:27977754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5158016/
Abstract

Recent studies have identified the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3B (APOBEC3B) as a source of mutations in various malignancies. APOBEC3B is overexpressed in several human cancer types, including breast cancer. In this study, we analyzed APOBEC3B mRNA expression in 305 primary breast cancers of Japanese women using quantitative reverse transcription-PCR, and investigated the relationships between the APOBEC3B mRNA expression and clinicopathological characteristics, prognosis, and TP53 mutations. The expression of APOBEC3B mRNA was detected in 277 tumors and not detected in 28 tumors. High APOBEC3B mRNA expression was significantly correlated with ER- and PR-negativity, high grade and high Ki67 index. The APOBEC3B mRNA expression was highest in the triple-negative and lowest in the hormone receptor-positive/HER2-negative subtypes. The TP53 gene was more frequently mutated in the tumors with high APOBEC3B mRNA expression. High APOBEC3B mRNA expression was significantly associated with poor recurrence-free survival in all cases and the ER-positive cases. These findings were almost consistent with the previous reports from the Western countries. In conclusion, high APOBEC3B mRNA expression was related to the aggressive phenotypes of breast cancer, high frequency of TP53 mutation and poor prognosis, especially in ER-positive tumors.

摘要

最近的研究已确定载脂蛋白B信使核糖核酸编辑酶催化多肽样3B(APOBEC3B)是各种恶性肿瘤中突变的一个来源。APOBEC3B在包括乳腺癌在内的几种人类癌症类型中过表达。在本研究中,我们使用定量逆转录聚合酶链反应分析了305例日本女性原发性乳腺癌中APOBEC3B信使核糖核酸的表达,并研究了APOBEC3B信使核糖核酸表达与临床病理特征、预后及TP53突变之间的关系。在277个肿瘤中检测到APOBEC3B信使核糖核酸的表达,在28个肿瘤中未检测到。APOBEC3B信使核糖核酸的高表达与雌激素受体和孕激素受体阴性、高级别及高Ki67指数显著相关。APOBEC3B信使核糖核酸表达在三阴性亚型中最高,在激素受体阳性/人表皮生长因子受体2阴性亚型中最低。在APOBEC3B信使核糖核酸高表达的肿瘤中,TP53基因更频繁地发生突变。APOBEC3B信使核糖核酸高表达在所有病例及雌激素受体阳性病例中均与无复发生存期差显著相关。这些发现与西方国家先前的报道几乎一致。总之,APOBEC3B信使核糖核酸高表达与乳腺癌的侵袭性表型、TP53突变的高频率及不良预后相关,尤其是在雌激素受体阳性肿瘤中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/5992796370f2/pone.0168090.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/3326346aa5d1/pone.0168090.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/7bf2301ecafa/pone.0168090.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/5992796370f2/pone.0168090.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/3326346aa5d1/pone.0168090.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/7bf2301ecafa/pone.0168090.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6210/5158016/5992796370f2/pone.0168090.g003.jpg

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本文引用的文献

1
Association of germline variants in the APOBEC3 region with cancer risk and enrichment with APOBEC-signature mutations in tumors.载脂蛋白B编辑酶催化多肽样蛋白3(APOBEC3)区域的种系变异与癌症风险的关联以及肿瘤中APOBEC特征性突变的富集
Nat Genet. 2016 Nov;48(11):1330-1338. doi: 10.1038/ng.3670. Epub 2016 Sep 19.
2
APOBEC3B high expression status is associated with aggressive phenotype in Japanese breast cancers.载脂蛋白B mRNA编辑酶催化多肽样3B(APOBEC3B)高表达状态与日本乳腺癌的侵袭性表型相关。
Breast Cancer. 2016 Sep;23(5):780-8. doi: 10.1007/s12282-015-0641-8. Epub 2015 Oct 17.
3
Molecular mechanism and clinical impact of APOBEC3B-catalyzed mutagenesis in breast cancer.
DNA 脱氨酶是人类 APOBEC3A 驱动的肝细胞癌在体内发生所必需的。
Int J Mol Sci. 2023 May 26;24(11):9305. doi: 10.3390/ijms24119305.
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APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential.APOBEC3 介导的癌症突变:原因、临床意义和治疗潜力。
J Hematol Oncol. 2023 Mar 28;16(1):31. doi: 10.1186/s13045-023-01425-5.
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APOBEC3B is overexpressed in cervical cancer and promotes the proliferation of cervical cancer cells through apoptosis, cell cycle, and p53 pathway.载脂蛋白B mRNA编辑酶催化多肽样蛋白3B(APOBEC3B)在宫颈癌中过表达,并通过凋亡、细胞周期和p53信号通路促进宫颈癌细胞增殖。
Front Oncol. 2022 Sep 29;12:864889. doi: 10.3389/fonc.2022.864889. eCollection 2022.
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Different members of the APOBEC3 family of DNA mutators have opposing associations with the landscape of breast cancer.DNA 突变体 APOBEC3 家族的不同成员与乳腺癌格局存在相反的关联。
Am J Cancer Res. 2021 Oct 15;11(10):5111-5125. eCollection 2021.
7
The von Hippel-Lindau Cullin-RING E3 ubiquitin ligase regulates APOBEC3 cytidine deaminases.von Hippel-Lindau Cullin-RING E3 泛素连接酶调节 APOBEC3 胞嘧啶脱氨酶。
Transl Res. 2021 Nov;237:1-15. doi: 10.1016/j.trsl.2021.05.002. Epub 2021 May 15.
8
GATA3 and APOBEC3B are prognostic markers in adrenocortical carcinoma and APOBEC3B is directly transcriptionally regulated by GATA3.GATA3和载脂蛋白B编辑酶催化多肽样3B(APOBEC3B)是肾上腺皮质癌的预后标志物,且APOBEC3B受GATA3直接转录调控。
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APOBEC3B expression in breast cancer cell lines and tumors depends on the estrogen receptor status.APOBEC3B 在乳腺癌细胞系和肿瘤中的表达依赖于雌激素受体状态。
Carcinogenesis. 2020 Aug 12;41(8):1030-1037. doi: 10.1093/carcin/bgaa002.
载脂蛋白B3(APOBEC3B)催化的乳腺癌诱变的分子机制及临床影响
Breast Cancer Res. 2015 Jan 21;17(1):8. doi: 10.1186/s13058-014-0498-3.
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APOBEC3 genes: retroviral restriction factors to cancer drivers.APOBEC3 基因:逆转录病毒限制因子到癌症驱动因子。
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Elevated APOBEC3B correlates with poor outcomes for estrogen-receptor-positive breast cancers.载脂蛋白B3(APOBEC3B)水平升高与雌激素受体阳性乳腺癌的不良预后相关。
Horm Cancer. 2014 Dec;5(6):405-13. doi: 10.1007/s12672-014-0196-8. Epub 2014 Aug 15.
7
TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance.乳腺癌中 TP53 突变谱具有亚型特异性,并具有明显的预后相关性。
Clin Cancer Res. 2014 Jul 1;20(13):3569-80. doi: 10.1158/1078-0432.CCR-13-2943. Epub 2014 May 6.
8
Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer.APOBEC3A 和 APOBEC3B 种系拷贝数多态性与乳腺癌中假定的 APOBEC 依赖性突变负担的关联。
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APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma.APOBEC3B 上调与浆液性卵巢癌的基因组突变模式。
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APOBEC3B mutagenesis in cancer.APOBEC3B 在癌症中的突变。
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