Supplementary Material for: Prognostic and clinical significance of the proliferation marker MCM7 in breast cancer

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 1156 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 basel-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 estrogen 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.

引言：微小染色体维持复合体组分7（Minichromosome maintenance complex component 7, MCM7）在癌细胞增殖与DNA复制过程中发挥至关重要的作用。然而，MCM7在乳腺癌（Breast Cancer, BC）中的表达特征及其预后意义仍有待明确。本研究旨在评估MCM7在乳腺癌中的作用。
方法：我们对1156例可手术早期乳腺癌样本开展MCM7的免疫组织化学染色，并利用公开可用的队列（n=13,430）在转录组水平对MCM7进行评估，并将MCM7的表达与包括Ki67标记指数、患者预后等临床病理参数进行相关性分析。
结果：在转录组水平，整个队列及管腔型乳腺癌亚组中，MCM7 mRNA高表达与患者生存期缩短存在显著关联，但在基底样分子亚型中未观察到该关联。43%的患者检测到MCM7蛋白高表达，且该表达与肿瘤侵袭性行为的相关临床病理特征显著相关。MCM7高表达与患者生存期缩短独立相关，尤其在雌激素受体阳性（管腔型）乳腺癌患者中更为显著。MCM7可将携带侵袭性临床病理特征的管腔型乳腺癌划分为不同的预后亚组。在接受内分泌治疗的乳腺癌患者中，MCM7高表达与不良预后相关，但该关联在接受辅助化疗的患者中不复存在。与单表达组相比，Ki67与MCM7均高表达的患者生存期最差，而两者均低表达的乳腺癌患者生存期最优。
结论：本研究结果表明，MCM7表达在乳腺癌中具有预后价值，可用于筛选可从辅助化疗中获益的管腔型乳腺癌患者。