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Transcriptomic and immunohistochemical approaches identify HLA-G as a predictive biomarker of gestational choriocarcinoma resistance to monochemotherapy
- Source :
- Gynecologic Oncology, Gynecologic Oncology, 2020, 158, pp.785-793. ⟨10.1016/j.ygyno.2020.05.042⟩, Gynecologic Oncology, Elsevier, 2020, 158, pp.785-793. ⟨10.1016/j.ygyno.2020.05.042⟩
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- International audience; 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.
- Subjects :
- 0301 basic medicine
[SDV]Life Sciences [q-bio]
HLA-G
Gestational choriocarcinoma
Malignant transformation
0302 clinical medicine
Pregnancy
Antineoplastic Combined Chemotherapy Protocols
Choriocarcinoma
reproductive and urinary physiology
Etoposide
Gestational trophoblastic neoplasia
Obstetrics and Gynecology
Hydatidiform Mole
Middle Aged
Immunohistochemistry
female genital diseases and pregnancy complications
3. Good health
[SDV] Life Sciences [q-bio]
Oncology
030220 oncology & carcinogenesis
Uterine Neoplasms
embryonic structures
Female
Chemoresistance
medicine.drug
Adult
Vincristine
Cyclophosphamide
Antineoplastic Agents
Young Adult
03 medical and health sciences
Predictive Value of Tests
Biomarkers, Tumor
medicine
Humans
HLA-G Antigens
business.industry
Hydatidiform moles
medicine.disease
Methotrexate
030104 developmental biology
Drug Resistance, Neoplasm
Cancer research
Transcriptome
business
Subjects
Details
- ISSN :
- 00908258 and 10956859
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Gynecologic Oncology
- Accession number :
- edsair.doi.dedup.....5c48cb09f80e04f6dd3e5ea42e100ffe
- Full Text :
- https://doi.org/10.1016/j.ygyno.2020.05.042