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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 613.
Published online Dec 16, 2009. doi:  10.1186/1471-2164-10-613
PMCID: PMC2810306
Increased epithelial stem cell traits in advanced endometrial endometrioid carcinoma
Shing-Jyh Chang,3,4 Tao-Yeuan Wang,5,6 Chan-Yen Tsai,1 Tzu-Fang Hu,1 Margaret Dah-Tsyr Chang,4 and Hsei-Wei Wangcorresponding author1,2,7
1Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
2VGH-YM Genome Research Center, National Yang-Ming University, Taipei, Taiwan
3Department of Obstetrics and Gynecology, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan
4Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
5Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan
6Mackay Medicine, Nursing and Management College, Taipei, Taiwan
7Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
corresponding authorCorresponding author.
Shing-Jyh Chang: justine3/at/ms8.hinet.net; Tao-Yeuan Wang: tywang/at/ms2.mmh.org.tw; Chan-Yen Tsai: chanyentw/at/yahoo.com.tw; Tzu-Fang Hu: yvonne74129/at/hotmail.com; Margaret Dah-Tsyr Chang: lscmdt/at/life.nthu.edu.tw; Hsei-Wei Wang: hwwang/at/ym.edu.tw
Received May 4, 2009; Accepted December 16, 2009.
Abstract
Background
It has been recognized cancer cells acquire characters reminiscent of those of normal stem cells, and the degree of stem cell gene expression correlates with patient prognosis. Lgr5(+) or CD133(+) epithelial stem cells (EpiSCs) have recently been identified and these cells are susceptible to neoplastic transformation. It is unclear, however, whether genes enriched in EpiSCs also contribute in tumor malignancy. Endometrial endometrioid carcinoma (EEC) is a dominant type of the endometrial cancers and is still among the most common female cancers. Clinically endometrial carcinoma is classified into 4 FIGO stages by the degree of tumor invasion and metastasis, and the survival rate is low in patients with higher stages of tumors. Identifying genes shared between advanced tumors and stem cells will not only unmask the mechanisms of tumor malignancy but also provide novel therapeutic targets.
Results
To identify EpiSC genes in late (stages III-IV) EECs, a molecular signature distinguishing early (stages I-II) and late EECs was first identified to delineate late EECs at the genomics level. ERBB2 and CCR1 were genes activated in late EECs, while APBA2 (MINT2) and CDK inhibitor p16 tumor suppressors in early EECs. MAPK pathway was significantly up in late EECs, indicating drugs targeting this canonical pathway might be useful for treating advanced EECs. A six-gene mini-signature was further identified to differentiate early from advanced EECs in both the training and testing datasets. Advanced, invasive EECs possessed a clear EpiSC gene expression pattern, explaining partly why these tumors are more malignant.
Conclusions
Our work provides new insights into the pathogenesis of EECs and reveals a previously unknown link between adult stem cells and the histopathological traits of EECs. Shared EpiSC genes in late EECs may contribute to the stem cell-like phenotypes shown by advanced tumors and hold the potential of being candidate therapeutic targets and novel prognosis biomarkers.
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