Transcriptomic Characterization of Postmolar Gestational Choriocarcinoma

Constance Collet,Jonathan Lopez,François Golfier,Nicolas Lemaitre,Nadia Alfaidy,Sophie Patrier,Pierre-Adrien Bolze,Christophe Battail,Benoit You,Fabienne Allias,Touria Hajri,Jérôme Massardier,François Mallet,Mojgan Devouassoux-Shisheboran

doi:10.3390/biomedicines9101474

Abstract

The human placenta shares properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion. However, the mechanisms that drive the evolution from premalignant proliferative placental diseases—called hydatidiform moles—to their malignant counterparts, gestational choriocarcinoma, as well as the factors underlying the increased aggressiveness of choriocarcinoma arising after term delivery compared to those developing from hydatidiform moles, are unknown. Using a 730-gene panel covering 13 cancer-associated canonical pathways, we compared the transcriptomic profiles of complete moles to those of postmolar choriocarcinoma samples and those of postmolar to post-term delivery choriocarcinoma. We identified 33 genes differentially expressed between complete moles and postmolar choriocarcinoma, which revealed TGF-β pathway dysregulation. We found the strong expression of SALL4, an upstream regulator of TGF-β, in postmolar choriocarcinoma, compared to moles, in which its expression was almost null. Finally, there were no differentially expressed genes between postmolar and post-term delivery choriocarcinoma samples. To conclude, the TGF-β pathway appears to be a crucial step in the progression of placental malignancies. Further studies should investigate the value of TGF- β family members as biomarkers and new therapeutic targets.

Highlights

The human placenta shares some properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion [1]
The PanCancer transcriptomic profiles used did not show any significant differences between postmolar and post-term choriocarcinoma; significant differences were observed, especially in the TGF-β large family, between complete molar pregnancies and subsequent postmolar choriocarcinoma. These results strongly suggest that term choriocarcinoma, despite being associated with a worse prognosis, should be considered from a transcriptomic point of view, to postmolar choriocarcinoma, at least regarding the present analysis
The bad prognosis associated with term choriocarcinoma may be explained by other factors, such as the increased delay in the diagnosis of a post-term choriocarcinoma compared to postmolar choriocarcinoma

Summary

Introduction

The human placenta shares some properties with solid tumors, such as rapid growth, tissue invasion, cell migration, angiogenesis, and immune evasion [1]. Whether these features of cancer emerged by selection or by the reactivation of embryonic pathways is currently unknown [1]. Studies assessing whether the genetic alterations seen in the neoplastic placenta, in choriocarcinoma, are epigenetically driven could provide important insights into the mechanisms that accompany the development of this cancer. As distinct from normal placental development, gestational trophoblastic diseases are a rare subset of placental conditions that include premalignant proliferations called partial or complete hydatidiform moles, and their invasive counterpart, named gestational trophoblastic neoplasia, of which choriocarcinoma is the most aggressive form. Choriocarcinoma following normal pregnancies are generally more severe and associated with an increased mortality compared to those arising from hydatidiform moles, but the determinants of its aggressiveness were poorly investigated [7]

Methods

Results

Conclusion