抑制复发性卵巢癌患者样本中的癌症干性 p21 调节 mRNA 和 microRNA 特征。
Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples.
机构信息
Department of Histopathology, University of Dublin, Trinity College, Trinity Centre for Health Sciences, St James' Hospital, Dublin 8, Ireland.
出版信息
J Ovarian Res. 2012 Jan 19;5(1):2. doi: 10.1186/1757-2215-5-2.
BACKGROUND
Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease.
METHODS
Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples.
RESULTS
Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component.
CONCLUSION
We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21 mechanism in ovarian disease. Targeting CSCs within ovarian cancer represents a potential therapeutic avenue.
背景
恶性卵巢疾病的死亡率很高，这是由于复发性耐药疾病的发生率很高。有传闻证据表明，这可能是由于癌症干细胞（CSC）的耐药特性所致。然而，我们对 CSC 在复发性卵巢疾病中的作用的理解仍然很少。在这项研究中，我们使用基因微阵列和对我们以前发表的 microRNA（miRNA）数据的荟萃分析来评估癌症干性特征在复发性卵巢疾病中的作用。
方法
使用微阵列分析来描述癌症干性胚胎癌细胞（EC）模型中的早期调控事件。然后将其与我们以前发表的原发性与复发性卵巢疾病研究的微阵列数据进行比较。同时，使用荟萃分析来鉴定肿瘤患者样本中的癌症干性 miRNA 特征。
结果
微阵列分析表明，参与早期调控的基因表达事件在鼠胚癌细胞（mEC）和胚胎干细胞（mES）之间存在 90%的差异。这与 mEC 和 mES 细胞在未分化和分化状态下的已知相似之处形成对比。基因列表比较鉴定了原发性与复发性数据中的癌症干性基因特征集，其中一部分是已知的 p53-p21 调节剂。该特征存在于原发性和复发性肿瘤中，或仅存在于原发性肿瘤中，但在复发性肿瘤中基本上不存在。miRNA 表达的荟萃分析显示，肿瘤样本中的癌症干性特征更明显。该 miRNA 特征再次与 p53-p21 调控相关，在复发性肿瘤中表达明显。我们的数据表明，卵巢癌中 p53-p21 的调控至少部分涉及癌症干性成分。
结论
我们提出了一个卵巢癌的 p53-p21 癌症干性特征模型。我们提出，这至少部分地以不同的方式调节卵巢疾病中的 p53-p21 机制。靶向卵巢癌中的 CSC 可能代表一种潜在的治疗途径。
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