不同受体状态的乳腺肿瘤中编码 ERα、ERβ、PR 和 HER2 的基因转录本水平的变化与绝经状态有关。

IF 2.8 3区 医学 Q2 ONCOLOGY Clinical & Translational Oncology Pub Date : 2024-11-04 DOI:10.1007/s12094-024-03777-x
Caglar Berkel
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引用次数: 0

摘要

背景:绝经前和绝经后乳腺癌患者的病因和预后各不相同。通过免疫组化(IHC)分析雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体 2(HER2)的表达状态,对预后存在巨大差异的乳腺癌分子亚型进行分类:方法:利用TCGA-BRCA项目的转录组学数据,在R编程环境下,根据绝经状态(绝经前与绝经后)分析不同受体状态的乳腺癌患者肿瘤中ESR1(编码ERα)、ESR2(编码ERβ)、PGR(编码PR)和ERBB2(编码HER2)的mRNA表达:结果发现:在ER阳性、PR阳性或HER2阴性的乳腺肿瘤中,绝经后女性肿瘤的ESR1转录物水平高于绝经前女性肿瘤;相反,绝经后女性肿瘤的ESR2转录物水平低于绝经前女性肿瘤。此外,绝经后妇女乳腺肿瘤中 PGR mRNA 的表达也低于绝经前妇女,仅在 ER + 或 PR + 状态的肿瘤中表达较高。根据三种受体的组合状态,还分析了绝经前和绝经后乳腺癌患者肿瘤中这些基因的表达情况:总之,研究结果表明,ESR1、ESR2 和 PGR 的 mRNA 表达可能因绝经状态的不同而在具有特定受体状态的乳腺肿瘤中有所不同。更重要的是,ESR1 和 ESR2 在乳腺癌患者绝经后的表达变化方向相反,这表明,考虑到这些受体在乳腺癌患者预后方面的高度临床重要性,有必要确定调节绝经后乳腺癌患者ER 同工酶不同方向表达的特定分子机制。
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Menopausal status-dependent alterations in the transcript levels of genes encoding ERα, ERβ, PR and HER2 in breast tumors with different receptor status.

Background: Breast cancer has distinct causes and prognoses in patients with premenopausal and postmenopausal status. The expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are analyzed by immunohistochemistry (IHC) to classify molecular subtypes of breast cancer among which large differences in prognosis exist.

Methods: The mRNA expression of ESR1 (encoding ERα), ESR2 (encoding ERβ), PGR (encoding PR), and ERBB2 (encoding HER2) was analyzed based on menopausal status (pre- vs post-menopausal) in tumors from breast cancer patients with different receptor status, in R programming environment, using transcriptomics data from TCGA-BRCA project.

Results: In ER-positive or PR-positive or HER2-negative breast tumors, ESR1 transcript levels were found to be higher in tumors from postmenopausal women than those from premenopausal women; in contrast, ESR2 transcript levels were lower in tumors from postmenopausal women than those from premenopausal women. Furthermore, PGR mRNA expression was lower in breast tumors from postmenopausal women than those from premenopausal women, only in those with ER + or PR + status. The expression of these genes between tumors from pre- and post-menopausal patients with breast cancer was also analyzed based on the combination of status of three receptors.

Conclusion: Together, the results suggest that mRNA expression of ESR1, ESR2, and PGR might differ depending on menopausal status in breast tumors with certain receptor status. More importantly, the change in the expression of ESR1 and ESR2 following menopause is in the opposite directions in breast cancer patients showing the need to identify particular molecular mechanisms regulating the expression of ER isoforms post-menopause in different directions in breast cancer patients, considering the high clinical importance of these receptors in terms of the prognosis of patients with breast cancer.

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来源期刊
CiteScore
6.20
自引率
2.90%
发文量
240
审稿时长
1 months
期刊介绍: Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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