Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients.
Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients.
复制标题
在412例患者的基于人群的队列中，乳腺癌的固有分子特征。
DOI：
10.1186/bcr1517
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发表时间：
2006
影响因子：
7.4
通讯作者：
Pawitan, Yudi
中科院分区：
文献类型：
--
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
分子标记及其所包含的丰富生物学信息在癌症诊断、预后和治疗预测方面具有巨大潜力。然而，到目前为止，它们尚未取代常规的组织病理学和分期标准，部分原因是对分子亚型进行的少数研究缺乏验证且临床特征有限。
我们获取了来自瑞典斯德哥尔摩和乌普萨拉基于人群的患者队列的412例乳腺癌的基因表达和临床数据。利用在挪威/斯坦福乳腺癌数据中得出的约500个基因的固有集合，我们验证了五种分子亚型——基底样、ERBB2、腔面A/B和正常样——的存在，并利用常规临床变量对这些亚型进行了广泛的特征描述。
我们发现，使用挪威/斯坦福特征对瑞典队列进行的质心预测与在瑞典队列内部进行的k -均值聚类之间总体一致性为77.5%。不一致分配率最高的情况出现在腔面A和腔面B亚型之间以及腔面B和ERBB2亚型之间。这些亚型在分级（p < 0.001）、p53突变（p < 0.001）和基因组不稳定性（p = 0.01）方面存在显著差异，但令人惊讶的是在淋巴结转移方面差异很小（p = 0.31）。此外，当前使用激素替代疗法的患者在正常样亚组中明显过多（p < 0.001）。对接受内分泌治疗的患者和未接受任何辅助治疗的患者分别进行分析，支持了先前的假设，即基底样亚型对辅助治疗有反应，而ERBB2和腔面B亚型反应较差。
我们发现乳腺癌的固有分子亚型广泛存在于来自瑞典基于人群的队列的不同患者群体中。最初为揭示稳定的肿瘤特征而选择的固有基因集被证明与进展相关的特性（如分级、p53突变和基因组不稳定性）具有很强的相关性。
Molecular markers and the rich biological information they contain have great potential for cancer diagnosis, prognostication and therapy prediction. So far, however, they have not superseded routine histopathology and staging criteria, partly because the few studies performed on molecular subtyping have had little validation and limited clinical characterization. We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables. We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders. We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3
作者：
Ploner A;Miller LD;Hall P;Bergh J;Pawitan Y
通讯作者：
Pawitan Y
影响因子：
3.9
作者：
Symmans, WF;Fiterman, DJ;Pusztai, L
通讯作者：
Pusztai, L
影响因子：
82.9
作者：
BERGH, J;NORBERG, T;HOLMBERG, L
通讯作者：
HOLMBERG, L
DOI：
10.1073/pnas.0932692100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Sorlie, T;Tibshirani, R;Botstein, D
通讯作者：
Botstein, D