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层粘连蛋白 A/C、B1 和 B 受体 mRNA 在人乳腺癌中的临床病理意义。

The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer.

机构信息

The London Breast Institute, Princess Grace Hospital, London, UK.

出版信息

Cell Mol Biol Lett. 2013 Dec;18(4):595-611. doi: 10.2478/s11658-013-0109-9. Epub 2013 Nov 30.

Abstract

Lamin A/C (LMNA), lamin B1 (LMNB1) and lamin B receptor (LBR) have key roles in nuclear structural integrity and chromosomal stability. In this study, we have studied the relationships between the mRNA expressions of A-type lamins, LMNB1 and LBR and the clinicopathological parameters in human breast cancer. Samples of breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT; n = 30) were assessed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher levels of A-type lamins and LMNB1 mRNA expression were seen in ANCT. Higher lamin A/C expression was associated with the early clinical stage (TNM1 vs. TNM3 - 13 vs. 0.21; p = 0.0515), with better clinical outcomes (disease-free survival vs. mortality - 11 vs. 1; p = 0.0326), and with better overall (p = 0.004) and disease-free survival (p = 0.062). The expression of LMNB1 declined with worsening clinical outcome (disease-free vs. mortalities - 0.0011 vs. 0.000; p = 0.0177). LBR mRNA expression was directly associated with tumor grade (grade 1 vs. grade 3 - 0.00 vs. 0.00; p = 0.0479) and Nottingham Prognostic Index (NPI1 vs. NPI3 - 0.00 vs. 0.00; p = 0.0551). To the best of our knowledge, this is the first study to suggest such a role for A-type lamins, lamin B1 and LBR in human breast cancer, identifying an important area for further research.

摘要

核纤层蛋白 A/C(LMNA)、核纤层蛋白 B1(LMNB1)和核纤层蛋白 B 受体(LBR)在核结构完整性和染色体稳定性方面发挥着关键作用。在这项研究中,我们研究了 A 型核纤层蛋白、LMNB1 和 LBR 的 mRNA 表达与人类乳腺癌临床病理参数之间的关系。使用逆转录和定量 PCR 评估了乳腺癌组织样本(n = 115)和相关非癌组织(ANCT;n = 30)的情况。分析了转录水平与临床病理数据的相关性。在 ANCT 中观察到 A 型核纤层蛋白和 LMNB1 mRNA 表达水平较高。核纤层蛋白 A/C 表达水平较高与早期临床分期(TNM1 与 TNM3-13 与 0.21;p = 0.0515)、较好的临床结局(无病生存率与死亡率-11 与 1;p = 0.0326)和更好的总体(p = 0.004)和无病生存率(p = 0.062)相关。LMNB1 的表达随临床结局恶化而下降(无病生存率与死亡率-0.0011 与 0.000;p = 0.0177)。LBR mRNA 表达与肿瘤分级(1 级与 3 级-0.00 与 0.00;p = 0.0479)和诺丁汉预后指数(NPI1 与 NPI3-0.00 与 0.00;p = 0.0551)直接相关。据我们所知,这是首次研究表明 A 型核纤层蛋白、核纤层蛋白 B1 和 LBR 在人类乳腺癌中发挥作用,这为进一步研究指明了重要方向。

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