Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy
Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy
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DOI：
10.1158/0008-5472.can-04-2696
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发表时间：
2004-12-01
期刊：
影响因子：
11.2
通讯作者：
Viens, P
中科院分区：
文献类型：
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作者：
Bertucci, F;Finetti, P;Viens, P
炎性乳腺癌 (IBC) 是一种罕见但具有侵袭性的乳腺癌，5 年生存率约为 40%。根据临床和/或病理标准进行诊断可能很困难。尚未确定最佳的全身新辅助治疗和病理反应的准确预测因子，以提高反应率和生存率。我们使用含有类似 8,000 个基因的 DNA 微阵列，对 81 名患者的乳腺癌样本进行了分析，其中 37 名患者患有 IBC，44 名患者患有非炎症性乳腺癌 (NIBC)。全局无监督层次聚类能够在一定程度上区分 IBC 和 NIBC 病例并揭示 IBC 的子类。监督分析确定了一个 109 个基因组，其表达可区分 IBC 和 NIBC 样本。该分子特征在包含 26 个样本的独立系列中得到验证，总体性能准确度为 85%。鉴别基因与可能与 IBC 侵袭性相关的各种细胞过程相关，包括信号转导、细胞运动、粘附和血管生成。类似的方法，通过留一法交叉验证，确定了一个 85 个基因组，将 IBC 患者分为具有显着不同的病理完全缓解率（一组为 70%，另一组为 0%）。这些结果表明基因表达谱有可能有助于更好地了解 IBC，并为 IBC 以及潜在的治疗靶点提供新的诊断和预测因素。
Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer with a 5-year survival limited to similar to40%. Diagnosis, based on clinical and/or pathological criteria, may be difficult. Optimal systemic neoadjuvant therapy and accurate predictors of pathological response have yet to be defined for increasing response rate and survival. Using DNA microarrrays containing similar to8,000 genes, we profiled breast cancer samples from 81 patients, including 37 with IBC and 44 with noninflammatory breast cancer (NIBC). Global unsupervised hierarchical clustering was able to some extent to distinguish IBC and NIBC cases and revealed subclasses of IBC. Supervised analysis identified a 109-gene set the expression of which discriminated IBC from NIBC samples. This molecular signature was validated in an independent series of 26 samples, with an overall performance accuracy of 85%. Discriminator genes were associated with various cellular processes possibly related to the aggressiveness of IBC, including signal transduction, cell motility, adhesion, and angiogenesis. A similar approach, with leave-one-out cross-validation, identified an 85-gene set that divided IBC patients with significantly different pathological complete response rate (70% in one group and 0% in the other group). These results show the potential of gene expression profiling to contribute to a better understanding of IBC, and to provide new diagnostic and predictive factors for IBC, as well as for potential therapeutic targets.