Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis
Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis
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DOI：
10.1186/1479-5876-10-121
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发表时间：
2012-06-11
影响因子：
7.4
通讯作者：
Rafii, Arash
中科院分区：
文献类型：
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作者：
Malek, Joel A.;Martinez, Alejandra;Rafii, Arash
背景：卵巢癌是妇科恶性肿瘤中死亡率最高的一种，因其诊断较晚，多为晚期，且主要累及腹膜。迄今为止，大多数研究都集中在原发性肿瘤。然而，预后与治疗结束时的残留疾病直接相关。因此，必须关注和研究卵巢癌中最常见的局限于腹膜腔的肉类转移性疾病的生物学。方法：我们使用高密度基因表达阵列来研究匹配的原发性和转移性之间的基因表达变化结果：我们发现腹膜转移癌的基因表达谱与原发癌相比有显著差异，这些变化与肿瘤的病理学特征有关。受潜在的拷贝数变异差异以及其他原因的影响。我们发现，差异表达的基因富集在特定的途径，包括JAK/STAT途径，细胞因子信号转导和其他免疫相关的途径。我们发现，潜在的拷贝数变异显着影响基因表达。事实上，在拷贝数变异的重要差异的患者表现出更大的基因表达差异之间的原发性和匹配的转移性lesions.Conclusions：我们的分析显示了一个非常具体的靶向在基因组和转录组水平上调某些途径在卵巢癌腹膜转移。此外，虽然原发性肿瘤使用某些途径，但我们确定了与转移性病变的明显差异。卵巢癌的个体化治疗应考虑原发灶与转移灶的差异。
Background: Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. To date most research has focused on primary tumor. However the prognosis is directly related to residual disease at the end of the treatment. Therefore it is mandatory to focus and study the biology of meatastatic disease that is most frequently localized to the peritoneal caivty in ovarian cancer.Methods: We used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal) lesions.Results: Here we show that gene expression profiles in peritoneal metastasis are significantly different than their matched primary tumor and these changes are affected by underlying copy number variation differences among other causes. We show that differentially expressed genes are enriched in specific pathways including JAK/STAT pathway, cytokine signaling and other immune related pathways. We show that underlying copy number variations significantly affect gene expression. Indeed patients with important differences in copy number variation displayed greater gene expression differences between their primary and matched metastatic lesions.Conclusions: Our analysis shows a very specific targeting at both the genomic and transcriptomic level to upregulate certain pathways in the peritoneal metastasis of ovarian cancer. Moreover, while primary tumors use certain pathways we identify distinct differences with metastatic lesions. The variation between primary and metastatic lesions should be considered in personalized treatment of ovarian cancer.