Background: Assembly factor for spindle microtubules (ASPM) has gained significant attention in cancer research due to its association with tumor growth and progression. Through the analysis of large-scale genomic datasets, ASPM has been identified as the top upregulated gene in breast cancer (BC), characterized by high proliferation. This multicohort study aimed to investigate the clinicopathological and prognostic significance of ASPM mRNA and protein expression in BC. Methods: ASPM mRNA expression was assessed using the Cancer Genome Atlas (TCGA) BC cohort and has been further validated in the Molecular Taxonomy of BC International Consortium (METABRIC) (n= 1980), The Uppsala cohort (n= 249), in addition to the combined multicentric cohort (n= 7252). ASPM protein expression was evaluated in a large BC cohort (n= 1300) using immunohistochemistry. The correlations between ASPM expression, clinicopathological parameters, molecular subtypes and outcome were assessed. The response to taxane treatment was compared to the clinical prognosis of ASPM using the ROC plotter. Results: High ASPM mRNA and protein expression were significantly associated with aggressive BC features and poor survival across all cohorts. The association with poor outcomes was maintained in the adjuvant chemotherapy and radio-therapy-treated patients. Responders to taxane treatment showed significantly elevated ASPM levels compared to non-responders. Conclusions: High ASPM expression predicts poor prognosis in BC. It may play a role in treatment resistance within a specific subgroup of patients. Further clinical trials are warranted to explore the potential of ASPM as a target for therapeutic interventions in cancer.
背景：纺锤体微管组装因子（ASPM）因其与肿瘤生长和进展的关联，在癌症研究中受到广泛关注。通过对大规模基因组数据集的分析，ASPM被确定为乳腺癌（BC）中上调最显著的基因，其特点是高增殖性。这项多队列研究旨在探讨ASPM mRNA和蛋白表达在乳腺癌中的临床病理学及预后意义。方法：利用癌症基因组图谱（TCGA）乳腺癌队列评估ASPM mRNA表达，并在乳腺癌国际分子分类联盟（METABRIC）（n=1980）、乌普萨拉队列（n=249）以及联合多中心队列（n=7252）中进一步验证。通过免疫组织化学方法在一个大型乳腺癌队列（n=1300）中评估ASPM蛋白表达。分析了ASPM表达与临床病理参数、分子亚型及预后的相关性。使用ROC绘图工具比较了紫杉烷类药物治疗反应与ASPM临床预后的关系。结果：在所有队列中，高ASPM mRNA和蛋白表达均与侵袭性乳腺癌特征及不良生存率显著相关。在接受辅助化疗和放疗的患者中，这种与不良预后的关联仍然存在。与无应答者相比，对紫杉烷类药物治疗有应答者的ASPM水平显著升高。结论：高ASPM表达预示乳腺癌预后不良，可能在特定患者亚群中参与治疗抵抗。需要进一步的临床试验来探索ASPM作为癌症治疗干预靶点的潜力。
Deciphering the Role of ASPM in Breast Cancer: A Comprehensive Multicohort Study
肿瘤(癌症)患者之家