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Int. J. Mol. Sci. 2017, 18(11), 2345; https://doi.org/10.3390/ijms18112345

Discovering the Deregulated Molecular Functions Involved in Malignant Transformation of Endometriosis to Endometriosis-Associated Ovarian Carcinoma Using a Data-Driven, Function-Based Analysis

1
School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
2
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan
3
Department of Medical Research, Taipei Veterans General Hospital, Taipei 112, Taiwan
4
Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan
5
Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 28 September 2017 / Revised: 3 November 2017 / Accepted: 4 November 2017 / Published: 6 November 2017
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Abstract

The clinical characteristics of clear cell carcinoma (CCC) and endometrioid carcinoma EC) are concomitant with endometriosis (ES), which leads to the postulation of malignant transformation of ES to endometriosis-associated ovarian carcinoma (EAOC). Different deregulated functional areas were proposed accounting for the pathogenesis of EAOC transformation, and there is still a lack of a data-driven analysis with the accumulated experimental data in publicly-available databases to incorporate the deregulated functions involved in the malignant transformation of EOAC. We used the microarray gene expression datasets of ES, CCC and EC downloaded from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) database. Then, we investigated the pathogenesis of EAOC by a data-driven, function-based analytic model with the quantified molecular functions defined by 1454 Gene Ontology (GO) term gene sets. This model converts the gene expression profiles to the functionome consisting of 1454 quantified GO functions, and then, the key functions involving the malignant transformation of EOAC can be extracted by a series of filters. Our results demonstrate that the deregulated oxidoreductase activity, metabolism, hormone activity, inflammatory response, innate immune response and cell-cell signaling play the key roles in the malignant transformation of EAOC. These results provide the evidence supporting the specific molecular pathways involved in the malignant transformation of EAOC. View Full-Text
Keywords: endometriosis; ovarian carcinoma; function-based; data-driven analysis; microarray gene expression datasets; Gene Ontology endometriosis; ovarian carcinoma; function-based; data-driven analysis; microarray gene expression datasets; Gene Ontology
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Chang, C.-M.; Yang, Y.-P.; Chuang, J.-H.; Chuang, C.-M.; Lin, T.-W.; Wang, P.-H.; Yu, M.-H.; Chang, C.-C. Discovering the Deregulated Molecular Functions Involved in Malignant Transformation of Endometriosis to Endometriosis-Associated Ovarian Carcinoma Using a Data-Driven, Function-Based Analysis. Int. J. Mol. Sci. 2017, 18, 2345.

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