Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
Identification of novel biomarkers associated with poor patient outcomes in invasive breast carcinoma
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DOI：
10.1007/s13277-016-5133-8
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发表时间：
2016-10-01
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影响因子：
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通讯作者：
Reis, Eduardo M.
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文献类型：
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作者：
Canevari, Renata A.;Marchi, Fabio A.;Reis, Eduardo M.
乳腺癌（BC）占女性所有癌症的23%，全球每年新发病例138万例，死亡46万例。尽管在识别原发性BC的分子标记物和不同治疗方式方面取得了重大进展，但预测其转移行为的能力仍然有限。本研究的目的是确定与巴西BC患者队列中不同临床结局相关的新分子标志物。我们使用来自24例浸润性导管BC患者的肿瘤样本生成了全球基因表达谱，这些患者至少随访了5年，其中包括一组15例预后良好的患者和另一组9例发生转移的患者。我们发现了一组58个差异表达基因（p < 0.01）。根据无病生存期和总生存期对独立的BC患者数据集进行分层的能力证实了这种转移标志的预后价值。通过定量逆转录聚合酶链反应（RT-qPCR）在一个独立的BC患者样本（47例预后良好，8例出现转移）中证实了预后不良患者中B3 GNT 7、PPM 1D、TNKS 2、PHB和GTSE 1的上调。通过免疫组织化学在1276个BC组织样本中测定BCL 2相关的细胞死亡激动剂（BAD）蛋白的表达，并且与寡核苷酸阵列数据中观察到的转移病例中降低的BAD mRNA表达水平一致。这些发现指出了新的预后标志物，可以区分具有转移潜力的乳腺癌和具有良好预后的乳腺癌。
Breast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38 million new cases and 460,000 deaths worldwide annually. Despite the significant advances in the identification of molecular markers and different modalities of treatment for primary BC, the ability to predict its metastatic behavior is still limited. The purpose of this study was to identify novel molecular markers associated with distinct clinical outcomes in a Brazilian cohort of BC patients. We generated global gene expression profiles using tumor samples from 24 patients with invasive ductal BC who were followed for at least 5 years, including a group of 15 patients with favorable outcomes and another with nine patients who developed metastasis. We identified a set of 58 differentially expressed genes (p aecurrency sign 0.01) between the two groups. The prognostic value of this metastasis signature was corroborated by its ability to stratify independent BC patient datasets according to disease-free survival and overall survival. The upregulation of B3GNT7, PPM1D, TNKS2, PHB, and GTSE1 in patients with poor outcomes was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in an independent sample of patients with BC (47 with good outcomes and eight that presented metastasis). The expression of BCL2-associated agonist of cell death (BAD) protein was determined in 1276 BC tissue samples by immunohistochemistry and was consistent with the reduced BAD mRNA expression levels in metastatic cases, as observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinomas with metastatic potential from those with favorable outcomes.