Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles

Jennifer R. King, Melissa L. Wilson, Szabolcs Hetey, Peter Kiraly, Koji Matsuo, Antonio V. Castaneda, Eszter Toth, Tibor Krenacs, Petronella Hupuczi, Paulette Mhawech-Fauceglia, Andrea Balogh, Andras Szilagyi, Janos Matko, Zoltan Papp, Lynda D. Roman, Victoria K. Cortessis, Nandor Gabor Than

Research output: Article

Abstract

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.

Original languageEnglish
JournalInternational journal of molecular sciences
Volume20
Issue number20
DOIs
Publication statusPublished - okt. 10 2019

Fingerprint

Hydatidiform Mole
Genes
genes
RNA
Galectins
Placenta
Tissue
Microarrays
Gene expression
Paraffin
Paraffins
gene expression
Histone Demethylases
paraffins
Proteins
Cytokine Receptors
Bioinformatics
proteins
methylation
Gene Expression

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles. / King, Jennifer R.; Wilson, Melissa L.; Hetey, Szabolcs; Kiraly, Peter; Matsuo, Koji; Castaneda, Antonio V.; Toth, Eszter; Krenacs, Tibor; Hupuczi, Petronella; Mhawech-Fauceglia, Paulette; Balogh, Andrea; Szilagyi, Andras; Matko, Janos; Papp, Zoltan; Roman, Lynda D.; Cortessis, Victoria K.; Than, Nandor Gabor.

In: International journal of molecular sciences, Vol. 20, No. 20, 10.10.2019.

Research output: Article

King, JR, Wilson, ML, Hetey, S, Kiraly, P, Matsuo, K, Castaneda, AV, Toth, E, Krenacs, T, Hupuczi, P, Mhawech-Fauceglia, P, Balogh, A, Szilagyi, A, Matko, J, Papp, Z, Roman, LD, Cortessis, VK & Than, NG 2019, 'Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles', International journal of molecular sciences, vol. 20, no. 20. https://doi.org/10.3390/ijms20204999
King, Jennifer R. ; Wilson, Melissa L. ; Hetey, Szabolcs ; Kiraly, Peter ; Matsuo, Koji ; Castaneda, Antonio V. ; Toth, Eszter ; Krenacs, Tibor ; Hupuczi, Petronella ; Mhawech-Fauceglia, Paulette ; Balogh, Andrea ; Szilagyi, Andras ; Matko, Janos ; Papp, Zoltan ; Roman, Lynda D. ; Cortessis, Victoria K. ; Than, Nandor Gabor. / Dysregulation of Placental Functions and Immune Pathways in Complete Hydatidiform Moles. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 20.
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abstract = "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.",
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AU - Wilson, Melissa L.

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AU - Kiraly, Peter

AU - Matsuo, Koji

AU - Castaneda, Antonio V.

AU - Toth, Eszter

AU - Krenacs, Tibor

AU - Hupuczi, Petronella

AU - Mhawech-Fauceglia, Paulette

AU - Balogh, Andrea

AU - Szilagyi, Andras

AU - Matko, Janos

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AU - Cortessis, Victoria K.

AU - Than, Nandor Gabor

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N2 - 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.

AB - 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.

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KW - galectin

KW - gestational trophoblastic disease

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KW - placental-specific gene

KW - systems biology

KW - trophoblast differentiation

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