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增殖标志物MCM7在乳腺癌中的预后及临床意义

Prognostic and Clinical Significance of the Proliferation Marker MCM7 in Breast Cancer.

作者信息

Lashen Ayat G, Toss Michael S, Rutland Catrin S, Green Andrew R, Mongan Nigel P, Rakha Emad

机构信息

Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, Nottingham, UK,

Department of Pathology, Faculty of Medicine, Menoufia University, Shebeen El Kom, Egypt,

出版信息

Pathobiology. 2025;92(1):18-27. doi: 10.1159/000540790. Epub 2024 Aug 27.

Abstract

INTRODUCTION

Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.

METHODS

We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome.

RESULTS

At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups.

CONCLUSION

The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.

INTRODUCTION

Minichromosome maintenance complex component 7 (MCM7) plays an essential role in proliferation and DNA replication of cancer cells. However, the expression and prognostic significance of MCM7 in breast cancer (BC) remain to be defined. In this study, we aimed to evaluate the role of MCM7 in BC.

METHODS

We conducted immunohistochemistry staining of MCM7 in 1,156 operable early-stage BC samples and assessed MCM7 at the transcriptomic levels using publicly available cohorts (n = 13,430). MCM7 expression was evaluated and correlated with clinicopathological parameters including Ki67 labelling index and patient outcome.

RESULTS

At the transcriptomic level, there was a significant association between high MCM7 mRNA levels and shorter patient survival in the whole cohort and in luminal BC class but not in the basal-like molecular subtype. High MCM7 protein expression was detected in 43% of patients and was significantly associated with parameters characteristic of aggressive tumour behaviour. MCM7 was independently associated with shorter survival, particularly in oestrogen receptor-positive (luminal) BC. MCM7 stratified luminal tumours with aggressive clinicopathological features into distinct prognostic groups. In endocrine therapy-treated BC patients, high MCM7 was associated with poor outcome, but such association disappeared with administration of adjuvant chemotherapy. Patients with high expression of Ki67 and MCM7 showed worst survival, while patients with double low expression BC showed the best outcome compared with single expression groups.

CONCLUSION

The current findings indicate that MCM7 expression has a prognostic value in BC and can be used to identify luminal BC patients who can benefit from adjuvant chemotherapy.

摘要

引言

微小染色体维持复合体组分7(MCM7)在癌细胞的增殖和DNA复制中起重要作用。然而,MCM7在乳腺癌(BC)中的表达及预后意义仍有待明确。在本研究中,我们旨在评估MCM7在BC中的作用。

方法

我们对1156例可手术的早期BC样本进行了MCM7免疫组化染色,并使用公开可用队列(n = 13430)在转录组水平评估MCM7。评估MCM7表达,并将其与包括Ki67标记指数和患者预后在内的临床病理参数相关联。

结果

在转录组水平上,高MCM7 mRNA水平与整个队列以及腔面型BC患者较短的生存期显著相关,但与基底样分子亚型无关。43%的患者检测到高MCM7蛋白表达,且其与侵袭性肿瘤行为特征参数显著相关。MCM7与较短生存期独立相关,尤其是在雌激素受体阳性(腔面型)BC中。MCM7将具有侵袭性临床病理特征的腔面型肿瘤分层为不同的预后组。在内分泌治疗的BC患者中,高MCM7与不良预后相关,但这种关联在辅助化疗后消失。Ki67和MCM7高表达的患者生存期最差,而双低表达BC患者与单表达组相比预后最佳。

结论

目前的研究结果表明,MCM7表达在BC中具有预后价值,可用于识别能从辅助化疗中获益的腔面型BC患者。

引言

微小染色体维持复合体组分7(MCM7)在癌细胞的增殖和DNA复制中起重要作用。然而,MCM7在乳腺癌(BC)中的表达及预后意义仍有待明确。在本研究中,我们旨在评估MCM7在BC中的作用。

方法

我们对1156例可手术的早期BC样本进行了MCM7免疫组化染色,并使用公开可用队列(n = 13430)在转录组水平评估MCM7。评估MCM7表达,并将其与包括Ki67标记指数和患者预后在内的临床病理参数相关联。

结果

在转录组水平上,高MCM7 mRNA水平与整个队列以及腔面型BC患者较短的生存期显著相关,但与基底样分子亚型无关。43%的患者检测到高MCM7蛋白表达,且其与侵袭性肿瘤行为特征参数显著相关。MCM7与较短生存期独立相关,尤其是在雌激素受体阳性(腔面型)BC中。MCM7将具有侵袭性临床病理特征的腔面型肿瘤分层为不同的预后组。在内分泌治疗的BC患者中,高MCM7与不良预后相关,但这种关联在辅助化疗后消失。Ki67和MCM7高表达的患者生存期最差,而双低表达BC患者与单表达组相比预后最佳。

结论

目前的研究结果表明,MCM7表达在BC中具有预后价值,可用于识别能从辅助化疗中获益的腔面型BC患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/760e/11797933/ff1464635605/pat-2025-0092-0001-540790_F01.jpg

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