Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy

Gynecol Oncol. 2020 Sep;158(3):785-793. doi: 10.1016/j.ygyno.2020.05.042. Epub 2020 Jun 5.

Abstract

Objective: Using a transcriptional approach on tissue samples, we sought to identify predictive biomarkers of post molar malignant transformation, and of choriocarcinoma chemosensitivity to mono- (methotrexate or actinomycin D) or polychemotherapy [EMA(Etoposide, Methotrexate, Actinomycin D)-CO(Cyclophosphamide, Vincristine) and EMA-EP(Etoposide, Cisplatine)] regimens.

Methods: We studied the expression of a 760-gene panel (PanCancer Pathway) related to oncogenesis and immune tolerance in tissue samples of complete hydatidiform moles and gestational choriocarcinoma.

Results: We did not identify any differentially expressed gene between moles with post molar malignant transformation in choriocarcinoma (n = 14) and moles with remission (n = 20). In monochemoresistant choriocarcinoma (n = 34), four genes (HLA-G, COL27A1, IL1R2 and GLI3) had a significantly reduced expression and one (THEM4) had an increased expression [FDR (false discovery rate) adjusted p-value ≤ 0.05] when compared to monochemosensitive choriocarcinoma (n = 9). The proportion of trophoblast cells and the intensity of immunohistochemical HLA-G expression were reduced in monochemoresistant choriocarcinoma (p < 0.05). In polychemoresistant choriocarcinoma (n = 20) we did not identify differentially expressed genes with an FDR adjusted p-value ≤ 0.05 when compared to polychemosensitive choriocarcinoma (n = 15). Gene pathway analysis revealed a predicted activation of IFN ᵞ in monochemoresistant choriocarcinoma and inhibited IL2 and TNF in polychemoresistant choriocarcinoma. The main biological functions predicted to be altered in chemoresistant choriocarcinoma were related to immunological homeostasis and leukopoiesis.

Conclusion: HLA-G is a strong candidate gene to predict choriocarcinoma resistance to monochemotherapy and that further studies are required to implement its routine quantification in the decision process for the management of gestational choriocarcinoma.

Keywords: Chemoresistance; Gestational choriocarcinoma; Gestational trophoblastic neoplasia; HLA-G; Hydatidiform moles; Methotrexate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Choriocarcinoma / drug therapy*
  • Choriocarcinoma / genetics*
  • Choriocarcinoma / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • HLA-G Antigens / genetics*
  • HLA-G Antigens / metabolism
  • Humans
  • Hydatidiform Mole / drug therapy*
  • Hydatidiform Mole / genetics*
  • Hydatidiform Mole / metabolism
  • Immunohistochemistry
  • Middle Aged
  • Predictive Value of Tests
  • Pregnancy
  • Transcriptome
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / genetics*
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • HLA-G Antigens