Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival.
Genomic profiling in locally advanced and inflammatory breast cancer and its link to DCE-MRI and overall survival.
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DOI：
10.3109/02656736.2015.1016557
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发表时间：
2015-06
期刊：
影响因子：
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通讯作者：
Dewhirst MW
中科院分区：
文献类型：
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作者：
Siamakpour-Reihani S;Owzar K;Jiang C;Scarbrough PM;Craciunescu OI;Horton JK;Dressman HK;Blackwell KL;Dewhirst MW
我们以前曾报道，从LABC患者新辅助治疗前获得的DCE-MRI灌注模式可预测病理临床反应。还对同一患者人群独立进行基因组分析。进行该回顾性研究以检验两个假设：i）基因表达谱与DCE-MRI灌注模式相关; ii）长期总生存数据与基因表达谱之间的关联可导致鉴定新的预测性生物标志物。我们利用RNA微阵列和DCE-MRI数据从47 LABC患者，包括13 IBC患者。通过Wilcoxon秩和检验确定基因表达谱与DCE-MRI灌注模式（离心和向心）之间的关联。使用考克斯等级评分检验评估基因表达水平与存活率之间的关联。对IBC亚群进行了额外的基因组分析，随访时间长达11年。在TCGA数据库中进一步评估基因表达与总生存率之间的关联。在离心和向心灌注模式之间观察到基因表达谱的差异：磺基转移酶家族，胞质，1A，苯酚偏好，成员1和2（SULT 1A 1，SULT 1A 2），聚（ADP-核糖）聚合酶，成员6（PARP 6）和转移肿瘤抗原1（MTA 1）。在IBC亚组中，我们的分析表明，45个基因的差异表达与长期生存相关。在这里，我们已经证明了DCE-MRI灌注模式和基因表达谱之间的关联。此外，我们还报道了IBC患者的候选预后生物标志物，其中一些基因与IBC和LABC的生存率显著相关。
We have previously reported that DCE-MRI perfusion patterns, obtained from LABC patients prior to neoadjuvant therapy, predicted pathologic clinical response. Genomic analyses were also independently conducted on the same patient population. This retrospective study was performed to test two hypotheses: i) gene expression profiles are associated with DCE-MRI perfusion patterns; ii) association between long term overall survival data and gene expression profiles can lead to identification of novel predictive biomarkers. We utilized RNA microarray and DCE-MRI data from 47 LABC patients, including 13 IBC patients. Association between gene expression profile and DCE-MRI perfusion patterns (centrifugal and centripetal) was determined by Wilcoxon rank sum test. Association between gene expression level and survival was assessed using a Cox rank score test. Additional genomic analysis of the IBC subset, with up to an 11-year period of follow-up, was conducted. Associations between gene expression and overall survival were further assessed in TCGA database. Differences in gene expression profiles were seen between centrifugal and centripetal perfusion patterns in the: sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1 and 2 (SULT1A1, SULT1A2), poly (ADP-ribose) polymerase, member 6 (PARP6), and metastasis tumor antigen1 (MTA1). In the IBC subset, our analyses demonstrated that differential expression of 45 genes was associated with long term survival. Here we have demonstrated an association between DCE-MRI perfusion patterns and gene expression profiles. In addition we have reported on candidate prognostic biomarkers in IBC patients, with some of the genes being significantly associated with survival in IBC and LABC.