利用基因表达谱对子宫内膜和卵巢同时发生的子宫内膜样肿瘤进行分期。

Use of gene expression profiles to stage concurrent endometrioid tumors of the endometrium and ovary.

作者信息

Guirguis Alfred, Elishaev Esther, Oh Sung-Hee, Tseng George C, Zorn Kristin, DeLoia Julie A

机构信息

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, PA, USA.

出版信息

Gynecol Oncol. 2008 Feb;108(2):370-6. doi: 10.1016/j.ygyno.2007.10.008.

Abstract

OBJECTIVE

The objectives of this study were to determine whether there are distinct gene expression profiles for endometrial and ovarian endometrioid carcinomas and to create a statistical model using these profiles to predict their organ of origin.

METHODS

Expression profiles of seven stage I, grades 1 and 2, endometrioid endometrial carcinomas and seven stage I ovarian endometrioid carcinomas were analyzed as the training set. The test set included seven advanced endometrial carcinomas and nine dual primary endometrial and ovarian primary tumors of endometrioid histology. Unsupervised hierarchical clustering, multidimensional scaling (MDS) and predictive analysis of microarrays (PAM) were used to analyze the data.

RESULTS

We identified 163 differentially expressed (DE) genes between endometrial and ovarian tumors. Both unsupervised hierarchical clustering and multidimensional scaling showed clear separation of the two groups. Pathway analysis of the 163 DE genes revealed significant biological differences between the two groups, which included metabolic and biosynthetic pathways. Further classification analysis on the training data using predictive analysis of microarray generated a 119-gene predictive model with 100% cross-validation accuracy. When the 119-gene model was applied to the test set of 16 samples, we found concordance in 11/16 samples and discordance in 5/16 samples with the pathologic classification.

CONCLUSION

We conclude that, although similar in histologic appearance, endometrioid carcinomas of the ovary and endometrium have distinct gene expression patterns. A larger test set is needed to prospectively evaluate this prediction model further.

摘要

目的

本研究的目的是确定子宫内膜样癌和卵巢子宫内膜样癌是否存在不同的基因表达谱,并利用这些谱创建一个统计模型来预测其起源器官。

方法

分析7例I期1级和2级子宫内膜样癌及7例I期卵巢子宫内膜样癌的表达谱作为训练集。测试集包括7例晚期子宫内膜癌和9例子宫内膜样组织学的双原发性子宫内膜和卵巢原发性肿瘤。采用无监督层次聚类、多维标度法(MDS)和微阵列预测分析(PAM)对数据进行分析。

结果

我们鉴定出子宫内膜肿瘤和卵巢肿瘤之间有163个差异表达基因。无监督层次聚类和多维标度法均显示两组明显分离。对这163个差异表达基因进行通路分析,发现两组之间存在显著的生物学差异,包括代谢和生物合成通路。使用微阵列预测分析对训练数据进行进一步分类分析,生成了一个119基因的预测模型,交叉验证准确率为100%。当将该119基因模型应用于16个样本的测试集时,我们发现11/16的样本结果与病理分类一致,5/16的样本结果不一致。

结论

我们得出结论,尽管卵巢和子宫内膜的子宫内膜样癌在组织学外观上相似,但它们具有不同的基因表达模式。需要更大的测试集来进一步前瞻性评估该预测模型。

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