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Open AccessArticle

Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles

1
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA
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Systems Biology of Reproduction Research Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary
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Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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First Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary
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Maternity Private Clinic of Obstetrics and Gynecology, H-1126 Budapest, Hungary
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Department of Immunology, Institute of Biology, Eotvos Lorand University, H-1117 Budapest, Hungary
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Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 4999; https://doi.org/10.3390/ijms20204999
Received: 17 September 2019 / Revised: 28 September 2019 / Accepted: 30 September 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Immunophenotyping in Autoimmune Diseases and Cancer)
Gene expression studies of molar pregnancy have been limited to a small number of candidate loci. We analyzed high-dimensional RNA and protein data to characterize molecular features of complete hydatidiform moles (CHMs) and corresponding pathologic pathways. CHMs and first trimester placentas were collected, histopathologically examined, then flash-frozen or paraffin-embedded. Frozen CHMs and control placentas were subjected to RNA-Seq, with resulting data and published placental RNA-Seq data subjected to bioinformatics analyses. Paraffin-embedded tissues from CHMs and control placentas were used for tissue microarray (TMA) construction, immunohistochemistry, and immunoscoring for galectin-14. Of the 14,022 protein-coding genes expressed in all samples, 3,729 were differentially expressed (DE) in CHMs, of which 72% were up-regulated. DE genes were enriched in placenta-specific genes (OR = 1.88, p = 0.0001), of which 79% were down-regulated, imprinted genes (OR = 2.38, p = 1.54 × 10−6), and immune genes (OR = 1.82, p = 7.34 × 10−18), of which 73% were up-regulated. DNA methylation-related enzymes and histone demethylases were dysregulated. “Cytokine–cytokine receptor interaction” was the most impacted of 38 dysregulated pathways, among which 17 were immune-related pathways. TMA-based immunoscoring validated the lower expression of galectin-14 in CHM. In conclusion, placental functions were down-regulated, imprinted gene expression was altered, and immune pathways were activated, indicating complex dysregulation of placental developmental and immune processes in CHMs. View Full-Text
Keywords: choriocarcinoma; hydatidiform mole; galectin; gestational trophoblastic disease; placental-specific gene; systems biology; trophoblast differentiation choriocarcinoma; hydatidiform mole; galectin; gestational trophoblastic disease; placental-specific gene; systems biology; trophoblast differentiation
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King, J.R.; Wilson, M.L.; Hetey, S.; Kiraly, P.; Matsuo, K.; Castaneda, A.V.; Toth, E.; Krenacs, T.; Hupuczi, P.; Mhawech-Fauceglia, P.; Balogh, A.; Szilagyi, A.; Matko, J.; Papp, Z.; Roman, L.D.; Cortessis, V.K.; Than, N.G. Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles. Int. J. Mol. Sci. 2019, 20, 4999.

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