Proteomic identification of predictive biomarkers for malignant transformation in complete hydatidiform moles

Placenta. 2019 Feb:77:58-64. doi: 10.1016/j.placenta.2019.02.004. Epub 2019 Feb 5.

Abstract

Introduction: Protein expression in cells are associated with oncogenesis. This study aims to explore proteomic profiles and discover potential biomarkers that can predict malignant transformation of hydatidiform mole.

Methods: Retrospective analysis was done in 14 cases of remission hydatidiform mole and 14 cases of hydatidiform mole who later developed malignancy (GTN group). Molar tissues were retrieved from -70 °C frozen tissue. Subsequently, a large-scale proteomic analysis was performed to identify proteins and compare their abundance levels in the preserved molar tissues from these two groups using a dimethyl-labeling technique coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: A total of 2,153 proteins were identified from all samples. 22 and 10 proteins were significantly up-regulated and down-regulated, respectively, in the GTN group compared with the mole group. These altered proteins were found in several biological groups such as cell-cell adhesion, secreted proteins, and ribonucleoproteins. Several hormone-related proteins were among the most up-regulated proteins in the GTN group including choriogonadotropin subunit beta (β-hCG) and alpha (α-hCG), growth/differentiation factor 15, as well as both pregnancy-specific beta-1-glycoproteins 2 and 3. In contrast, protein S100-A11 and l-lactate dehydrogenase A chain, were down-regulated in molar tissue from most patients in the GTN group.

Discussion: This study identified a set of differentially expressed proteins in molar tissues that could potentially be further examined as predictive biomarkers for the malignant transformation of CHMs. A molar proteome database was constructed and can be accessible online at http://sysbio.chula.ac.th/Database/GTD_DB/Supplementary_Data.xlsx.

Keywords: Gestational trophoblastic disease; Hydatidiform mole; Proteomics; Trophoblastic neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers, Tumor / metabolism*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism
  • Chromatography, Liquid
  • Down-Regulation
  • Female
  • Gestational Trophoblastic Disease / metabolism
  • Gestational Trophoblastic Disease / pathology
  • Glycoprotein Hormones, alpha Subunit / metabolism
  • Humans
  • Hydatidiform Mole / metabolism*
  • Hydatidiform Mole / pathology*
  • Hydatidiform Mole, Invasive / metabolism
  • Hydatidiform Mole, Invasive / pathology
  • Middle Aged
  • Pregnancy
  • Proteomics
  • Retrospective Studies
  • Tandem Mass Spectrometry
  • Up-Regulation
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CGA protein, human
  • Chorionic Gonadotropin, beta Subunit, Human
  • Glycoprotein Hormones, alpha Subunit