Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures.
Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures.
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DOI：
10.1186/bcr2124
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Delorenzi M
中科院分区：
文献类型：
--
作者：
Wirapati P;Sotiriou C;Kunkel S;Farmer P;Pradervand S;Haibe-Kains B;Desmedt C;Ignatiadis M;Sengstag T;Schütz F;Goldstein DR;Piccart M;Delorenzi M
通过基因表达谱对乳腺癌的亚型和预后进行了广泛的研究，导致了不同的特征，它们的组成基因几乎没有重叠。尽管先前的一项研究证明了基因表达特征之间的预后一致性，但它仅限于一个数据集，并且没有完全阐明不同基因之间的相互关系，也没有检查众所周知的乳腺癌肿瘤发生的生物学过程对其预后表现的贡献。为了解决上述问题并进一步验证这些初步发现，我们对可公开获得的乳腺癌基因表达和临床数据进行了最大规模的荟萃分析，这些数据包括2833个乳腺肿瘤。利用乳腺癌中三个关键生物学过程(即增殖、雌激素受体[ER]和HER2信号)的基因共表达模块，分析9个预后标志的组成基因的作用。使用荟萃分析方法，我们巩固了与ER信号、ERBB2扩增和增殖相关的信号。以前发表的乳腺癌固有亚型的表达命名法可以映射到三个模块，即ER-/HER2-(基本样型)，HER2+(HER2样型)，以及低和高增殖的ER+/HER2-亚型(腔A和B)。我们发现，在整个数据集中，所有九个预后信号都表现出相似的预后表现。它们的预后能力主要归因于对增殖活性的检测。虽然ER状态(基础状态)和ERBB2+表达状态对应于不良预后，但它们似乎是通过增殖基因的表达升高而起作用的，因此只包含关于预后的间接信息。衡量肿瘤进展程度的临床变量，如肿瘤大小和结节状态，仍然为增殖基因增加了独立的预后信息。这一荟萃分析统一了以往乳腺癌基因表达研究的各种结果。它揭示了传统预后因素、基于表达的亚型和预后标志之间的联系，强调了增殖在乳腺癌预后中的重要作用。
Breast cancer subtyping and prognosis have been studied extensively by gene expression profiling, resulting in disparate signatures with little overlap in their constituent genes. Although a previous study demonstrated a prognostic concordance among gene expression signatures, it was limited to only one dataset and did not fully elucidate how the different genes were related to one another nor did it examine the contribution of well-known biological processes of breast cancer tumorigenesis to their prognostic performance. To address the above issues and to further validate these initial findings, we performed the largest meta-analysis of publicly available breast cancer gene expression and clinical data, which are comprised of 2,833 breast tumors. Gene coexpression modules of three key biological processes in breast cancer (namely, proliferation, estrogen receptor [ER], and HER2 signaling) were used to dissect the role of constituent genes of nine prognostic signatures. Using a meta-analytical approach, we consolidated the signatures associated with ER signaling, ERBB2 amplification, and proliferation. Previously published expression-based nomenclature of breast cancer 'intrinsic' subtypes can be mapped to the three modules, namely, the ER-/HER2- (basal-like), the HER2+ (HER2-like), and the low- and high-proliferation ER+/HER2- subtypes (luminal A and B). We showed that all nine prognostic signatures exhibited a similar prognostic performance in the entire dataset. Their prognostic abilities are due mostly to the detection of proliferation activity. Although ER- status (basal-like) and ERBB2+ expression status correspond to bad outcome, they seem to act through elevated expression of proliferation genes and thus contain only indirect information about prognosis. Clinical variables measuring the extent of tumor progression, such as tumor size and nodal status, still add independent prognostic information to proliferation genes. This meta-analysis unifies various results of previous gene expression studies in breast cancer. It reveals connections between traditional prognostic factors, expression-based subtyping, and prognostic signatures, highlighting the important role of proliferation in breast cancer prognosis.
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在412例患者的基于人群的队列中，乳腺癌的固有分子特征。
影响因子：
7.4
作者：
Calza, Stefano;Hall, Per;Auer, Gert;Bjohle, Judith;Klaar, Sigrid;Kronenwett, Ulrike;T Liu, Edison;Miller, Lance;Ploner, Alexander;Smeds, Johanna;Bergh, Jonas;Pawitan, Yudi
通讯作者：
Pawitan, Yudi
影响因子：
50.3
作者：
Richardson, AL;Wang, ZGC;Ganesan, S
通讯作者：
Ganesan, S
影响因子：
8
作者：
Farmer, P;Bonnefoi, H;Iggo, R
通讯作者：
Iggo, R
影响因子：
9.8
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
通讯作者：
Brown PO
影响因子：
4.4
作者：
Hu, Zhiyuan;Fan, Cheng;Perou, Charles M.
通讯作者：
Perou, Charles M.