Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis.
Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis.
复制标题
DOI：
10.1186/gb-2013-14-4-r34
复制
发表时间：
2013-04-29
期刊：
影响因子：
12.3
通讯作者：
Miller LD
中科院分区：
文献类型：
--
作者：
Nagalla S;Chou JW;Willingham MC;Ruiz J;Vaughn JP;Dubey P;Lash TL;Hamilton-Dutoit SJ;Bergh J;Sotiriou C;Black MA;Miller LD
指示肿瘤增殖能力和肿瘤免疫细胞相互作用的基因表达特征已成为乳腺癌预后的主要生物学驱动预测因子。这些特征在生物学和预后方面如何相互关联仍有待澄清。为了研究增殖与免疫基因特征之间的关系，我们分析了1954个临床注释的乳腺肿瘤表达谱的集成数据集，随机分为训练集和测试集，以允许双向发现和验证基因与生存的关联。分层聚类揭示了大量具有已知免疫功能的远端无转移生存相关基因，这些基因进一步划分为三个不同的免疫元基因组，可能反映了B细胞和/或浆细胞；T细胞和自然杀伤细胞；单核细胞和/或树突状细胞。一个增殖元细胞允许病例分层成增殖三分之一。这些宏基因的预后强度主要局限于最高增殖三分之一的肿瘤，尽管在中低增殖三分之一中观察到内在的亚型特异性差异。在高度增殖的肿瘤中，高特异表达与转移风险显著降低相等，而三种免疫特异表达中的任何一种低特异表达的肿瘤与预后差相关，尽管其他两种特异表达较高。这些发现表明，肿瘤部位多种免疫细胞类型之间的有效相互作用以增殖依赖的方式促进了长期的抗转移性免疫。高增殖肿瘤中有效免疫应答者亚群的出现具有新的预后后果。
Gene expression signatures indicative of tumor proliferative capacity and tumor-immune cell interactions have emerged as principal biology-driven predictors of breast cancer outcomes. How these signatures relate to one another in biological and prognostic contexts remains to be clarified. To investigate the relationship between proliferation and immune gene signatures, we analyzed an integrated dataset of 1,954 clinically annotated breast tumor expression profiles randomized into training and test sets to allow two-way discovery and validation of gene-survival associations. Hierarchical clustering revealed a large cluster of distant metastasis-free survival-associated genes with known immunological functions that further partitioned into three distinct immune metagenes likely reflecting B cells and/or plasma cells; T cells and natural killer cells; and monocytes and/or dendritic cells. A proliferation metagene allowed stratification of cases into proliferation tertiles. The prognostic strength of these metagenes was largely restricted to tumors within the highest proliferation tertile, though intrinsic subtype-specific differences were observed in the intermediate and low proliferation tertiles. In highly proliferative tumors, high tertile immune metagene expression equated with markedly reduced risk of metastasis whereas tumors with low tertile expression of any one of the three immune metagenes were associated with poor outcome despite higher expression of the other two metagenes. These findings suggest that a productive interplay among multiple immune cell types at the tumor site promotes long-term anti-metastatic immunity in a proliferation-dependent manner. The emergence of a subset of effective immune responders among highly proliferative tumors has novel prognostic ramifications.
登录
查看更多内容
影响因子：
5.4
作者：
Agematsu, K;Nagumo, H;Komiyama, A
通讯作者：
Komiyama, A
影响因子：
45.3
作者：
Bianchini, Giampaolo;Qi, Yuan;Pusztai, Lajos
通讯作者：
Pusztai, Lajos
影响因子：
--
作者：
Baier, PK;Wimmenauer, S;Farthmann, EH
通讯作者：
Farthmann, EH
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
11.2
作者：
Dai, HY;van't Veer, L;Friend, S
通讯作者：
Friend, S