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首页> 外文期刊>BMC Medical Genomics >Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells
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Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells

机译：基因表达谱支持以下假设：人卵巢表面上皮细胞是多能的并且能够充当卵巢癌起始细胞

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Background Accumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE) and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube. Methods Comparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI) isolated by laser capture micro-dissection (LCM) from human serous papillary ovarian adenocarcinomas. The results of the gene expression analyses were randomly confirmed in paraffin embedded tissues from ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using immunohistochemistry. Differentially expressed genes were analyzed using gene ontology, molecular pathway, and gene set enrichment analysis algorithms. Results Consistent with multipotent capacity, genes in pathways previously associated with adult stem cell maintenance are highly expressed in ovarian surface epithelia and are not expressed or expressed at very low levels in serous ovarian adenocarcinoma. Among the over 2000 genes that are significantly differentially expressed, a number of pathways and novel pathway interactions are identified that may contribute to ovarian adenocarcinoma development. Conclusions Our results are consistent with the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as the origin of ovarian adenocarcinoma. While our findings do not rule out the possibility that ovarian cancers may also arise from other sources, they are inconsistent with claims that ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating cells.
机译：背景技术越来越多的证据表明，体干细胞会发生诱变转化为癌症引发细胞。有人认为人类卵巢浆液性浆液亚型是由至少两种可能的祖细胞类型引起的：卵巢表面上皮细胞（OSE）和/或仍处于输卵管远端的尚未定义的祖细胞类型。方法对从正常人卵巢表面去除的OSE和通过激光捕获显微解剖（LCM）从人浆液性乳头状卵巢腺癌中分离的卵巢癌上皮细胞（CEPI）进行比较基因表达谱分析。使用免疫组织化学方法，在浆液性亚型的卵巢腺癌和非肿瘤性卵巢组织的石蜡包埋组织中随机确认了基因表达分析的结果。使用基因本体论，分子途径和基因组富集分析算法分析差异表达的基因。结果与多能能力一致，以前与成体干细胞维持相关的途径中的基因在卵巢表面上皮细胞中高表达，而在浆液性卵巢腺癌中不表达或表达水平很低。在明显差异表达的2000多个基因中，鉴定了许多可能有助于卵巢腺癌发展的途径和新颖的途径相互作用。结论我们的结果与人卵巢表面上皮细胞多能并能够作为卵巢腺癌起源的假说相符。尽管我们的发现并不排除卵巢癌也可能来自其他来源的可能性，但它们与认为卵巢表面上皮细胞不能作为卵巢癌起始细胞起源的说法不一致。

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