Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, N-5021, Norway.
Sci Rep. 2020 Feb 19;10(1):2914. doi: 10.1038/s41598-020-59728-3.
Studies indicate that stathmin expression associates with PI3K activation in breast cancer, suggesting stathmin as a marker for targetable patient subgroups. Here we assessed stathmin in relation to tumour proliferation, vascular and immune responses, BRCA1 germline status, basal-like differentiation, clinico-pathologic features, and survival. Immunohistochemical staining was performed on breast cancers from two series (cohort 1, n = 187; cohort 2, n = 198), and mass spectrometry data from 24 cases and 12 breast cancer cell lines was examined for proteomic profiles. Open databases were also explored (TCGA, METABRIC, Oslo2 Landscape cohort, Cancer Cell Line Encyclopedia). High stathmin expression associated with tumour proliferation, p53 status, basal-like differentiation, BRCA1 genotype, and high-grade histology. These patterns were confirmed using mRNA data. Stathmin mRNA further associated with tumour angiogenesis, immune responses and reduced survival. By logistic regression, stathmin protein independently predicted a BRCA1 genotype (OR 10.0, p = 0.015) among ER negative tumours. Cell line analysis (Connectivity Map) implied PI3K inhibition in tumours with high stathmin. Altogether, our findings indicate that stathmin might be involved in the regulation of tumour angiogenesis and immune responses in breast cancer, in addition to tumour proliferation. Cell data point to potential effects of PI3K inhibition in tumours with high stathmin expression.
研究表明,stathmin 的表达与乳腺癌中的 PI3K 激活相关,提示 stathmin 可作为靶向治疗患者亚组的标志物。在这里,我们评估了 stathmin 与肿瘤增殖、血管和免疫反应、BRCA1 种系状态、基底样分化、临床病理特征和生存的关系。对两个系列(队列 1,n=187;队列 2,n=198)的乳腺癌进行了免疫组织化学染色,并对 24 例和 12 例乳腺癌细胞系的质谱数据进行了蛋白质组学分析。还探索了开放数据库(TCGA、METABRIC、Oslo2 景观队列、癌症细胞系百科全书)。高 stathmin 表达与肿瘤增殖、p53 状态、基底样分化、BRCA1 基因型和高级别组织学相关。这些模式使用 mRNA 数据得到了证实。Stathmin mRNA 进一步与肿瘤血管生成、免疫反应和降低的生存相关。通过逻辑回归,stathmin 蛋白独立预测了 ER 阴性肿瘤中的 BRCA1 基因型(OR 10.0,p=0.015)。细胞系分析(连接映射)暗示在高 stathmin 表达的肿瘤中存在 PI3K 抑制。总的来说,我们的研究结果表明,stathmin 可能参与乳腺癌中肿瘤血管生成和免疫反应的调节,除了肿瘤增殖。细胞数据表明,在高 stathmin 表达的肿瘤中,PI3K 抑制可能具有潜在的作用。