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

• Published in: Gynecologic oncology 2020-09, Vol.158 (3), p.785-793
• Main Authors: Bolze, Pierre-Adrien, Lopez, Jonathan, Allias, Fabienne, Hajri, Touria, Patrier, Sophie, Devouassoux-Shisheboran, Mojgan, Massardier, Jérôme, You, Benoit, Golfier, François, Mallet, François
• Format: Article
• Language: English
• Subjects: 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; Chemoresistance; Choriocarcinoma - drug therapy; Choriocarcinoma - genetics; Choriocarcinoma - metabolism; Drug Resistance, Neoplasm; Female; Gestational choriocarcinoma; Gestational trophoblastic neoplasia; HLA-G; HLA-G Antigens - genetics; HLA-G Antigens - metabolism; Humans; Hydatidiform Mole - drug therapy; Hydatidiform Mole - genetics; Hydatidiform Mole - metabolism; Hydatidiform moles; Immunohistochemistry; Life Sciences; Methotrexate; Middle Aged; Predictive Value of Tests; Pregnancy; Transcriptome; Uterine Neoplasms - drug therapy; Uterine Neoplasms - genetics; Young Adult
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2020.05.042

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. 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. 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