School of Biology, Georgia Institute of Technology, Atlanta, GA, USA.
BMC Med Genomics. 2009 Dec 29;2:71. doi: 10.1186/1755-8794-2-71.
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.
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.
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.
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.
越来越多的证据表明，体干细胞经历诱变转化为癌症起始细胞。人类浆液性卵巢腺癌被假设至少有两种可能的祖细胞来源：卵巢表面上皮（OSE）和/或尚未定义的一类位于输卵管末端的祖细胞。
对从正常人类卵巢表面去除的 OSE 和通过激光捕获微切割（LCM）从人类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。使用免疫组织化学技术，在浆液性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基因表达分析的结果。使用基因本体、分子途径和基因集富集分析算法分析差异表达基因。
与多能性一致，与成人干细胞维持相关的途径中的基因在卵巢表面上皮中高度表达，而在浆液性卵巢腺癌中不表达或表达水平非常低。在 2000 多个显著差异表达的基因中，确定了一些可能有助于卵巢腺癌发展的途径和新的途径相互作用。
我们的结果与卵巢表面上皮是多能的并且能够作为卵巢腺癌起源的假说一致。虽然我们的发现不排除卵巢癌也可能起源于其他来源的可能性，但与卵巢表面上皮不能作为卵巢癌起始细胞起源的说法不一致。
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