The humoral immune system has a key prognostic impact in node-negative breast cancer
The humoral immune system has a key prognostic impact in node-negative breast cancer
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DOI：
10.1158/0008-5472.can-07-5206
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发表时间：
2008-07-01
期刊：
影响因子：
11.2
通讯作者：
Gehrmann, Mathias
中科院分区：
文献类型：
--
作者：
Schmidt, Marcus;Boehm, Daniel;Gehrmann, Mathias
雌激素受体（ER）表达和增殖活性是乳腺癌的既定预后因素。在寻找其他预后基序的过程中，我们使用发现方法分析了手术后未接受全身治疗的患者的200个肿瘤的基因表达模式。在进行层次聚类分析后，我们确定了与增殖、类固醇激素受体表达以及B细胞和T细胞浸润的生物学过程相关的共调节基因。我们计算了多基因作为一个特定的集群内包含的所有基因的替代品，并可视化的相对表达与转移的时间与主成分分析。不同的模式导致了免疫系统在具有高表达增殖相关基因的肿瘤中的预后作用的假设。在多变量考克斯回归分析中，增殖多基因显示与整个发现队列的无转移生存率显著相关[风险比（HR），2.20; 95%置信区间（95% CI），1.40 - 3.46]。B细胞多基因在具有高增殖活性的癌中显示了额外的独立预后信息（HR，0.66; 95%CI，0.46 - 0.97）。B细胞多基因的预后影响通过多变量分析在富集高级别肿瘤的第一验证队列（n = 286; HR，0.78; 95%CI，0.62 - 0.98）和富集年轻患者的第二验证队列（n = 302; 1111，0.83; 95%CI，0.7 - 0.97）中独立证实。因此，我们可以在三组未经治疗的淋巴结阴性乳腺癌患者中表明，不道德免疫系统在乳腺癌的无转移生存中起着关键作用。
Estrogen receptor (ER) expression and proliferative activity are established prognostic factors in breast cancer. In a search for additional prognostic motifs, we analyzed the gene expression patterns of 200 tumors of patients who were not treated by systemic therapy after surgery using a discovery approach. After performing hierarchical cluster analysis, we identified coregulated genes related to the biological process of proliferation, steroid hormone receptor expression, as well as B-cell and T-cell infiltration. We calculated metagenes as a surrogate for all genes contained within a particular cluster and visualized the relative expression in relation to time to metastasis with principal component analysis. Distinct patterns led to the hypothesis of a prognostic role of the immune system in tumors with high expression of proliferation-associated genes. In multivariate Cox regression analysis, the proliferation metagene showed a significant association with metastasis-free survival of the whole discovery cohort [hazard ratio (HR), 2.20; 95% confidence interval (95% CI), 1.40-3.46]. The B-cell metagene showed additional independent prognostic information in carcinomas with high proliferative activity (HR, 0.66; 95% CI, 0.46-0.97). A prognostic influence of the B-cell metagene was independently confirmed by multivariate analysis in a first validation cohort enriched for high-grade tumors (n = 286; HR, 0.78; 95%) CI, 0.62-0.98) and a second validation cohort enriched for younger patients (n = 302; 1111, 0.83; 95% CI, 0.7-0.97). Thus, we could show in three cohorts of untreated, node-negative breast cancer patients that the Immoral immune system plays a pivotal role in metastasis-free survival of carcinomas of the breast.