Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival
Gene expression profiles of inflammatory breast cancer: correlation with response to neoadjuvant chemotherapy and metastasis-free survival
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DOI：
10.1093/annonc/mdt496
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发表时间：
2014-02-01
影响因子：
50.5
通讯作者：
Van Laere, S. J.
中科院分区：
文献类型：
--
作者：
Bertucci, F.;Ueno, N. T.;Van Laere, S. J.
我们分析了前所未有数量的137个IBC样本的基因表达谱，并确定了与新辅助化疗病理完全反应相关的107个基因签名。该特征具有生物学相关性，并在三个独立的组中得到验证，包括两个IBC组和一个非IBC组，在两个验证组中具有独立的显著预测值。没有发现与无转移生存相关的强有力的特征。炎性乳腺癌（IBC）是一种侵袭性疾病。迄今为止，没有分子特征可靠地预测化疗（CT）的反应或生存。利用DNA微阵列技术，我们寻找了多基因预测因子，世界IBC联盟对137个IBC和252个非IBC样本进行了全基因组表达谱分析。我们在87和106个信息性IBC样本的相应子集中搜索与对基于蒽环类药物的新辅助CT的病理完全应答（pCR）和无远处转移生存（DMFS）相关的转录谱。相关性进行了研究，预测和预后的基因表达签名发表在nIBC（nIBC-GES）。监督分析测试了19种生物学途径和234种转录因子的基因和激活特征，五种中的三种测试了预后性nIBC-GES，两种测试了预测性nIBC-GES区分了有和没有pCR的IBC，以及两种干扰素激活特征。我们确定了一个富含免疫相关基因的107个基因签名，用于区分IBC中的应答者和非应答者。通过3个独立集（2个IBC集和1个nIBC集）的外部验证证明了该模型的稳健性，在多变量分析中，IBC和nIBC验证集具有独立的显著预测值。我们没有发现与IBC患者DMFS相关的强有力的特征，并且测试的预后GES和分子亚型都没有提供信息，而它们在我们的nIBC系列中（220个I-III期信息样本）。尽管样本量相对较小，但我们发现IBC对新辅助CT的反应与nIBC一样，与免疫相关过程相关，提示存在负责pCR的类似机制。一个更大的IBC系列分析是必要的基因表达谱和DMFS的相关性。
We analyzed gene expression profiles of an unprecedented number of 137 IBC samples and identified a 107-gene signature associated with pathological complete response to neoadjuvant chemotherapy. This signature was biologically relevant and validated in three independent sets including two IBC sets and one non-IBC set, with independent significant predictive value in both validation sets. No robust signature related to metastasis-free survival was found.Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors.The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors.Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I-III informative samples).Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.