完全性葡萄胎 (CHM) 是一种常见疾病，已知会发展为葡萄胎后妊娠滋养细胞肿瘤 (GTN)。然而，CHM 进展为磨牙后 GTN 的分子机制仍然很大程度上未知。在这项研究中，我们使用 RNA-seq 研究了与进展相关的分子因素。我们纳入了 13 名 CHM 患者，并使用新鲜冷冻的样本进行了 RNA-seq。我们鉴定了发生 GTN 的患者（GTN 组）和清宫后自发缓解的患者（SR 组）之间的差异表达基因，并进行了通路分析。然后，对绒毛膜癌（JAR 和 JEG-3）和 CHM（Hmol1-3B 和 Hmol1-2C）细胞进行功能分析。此外，我们评估了XBP1过表达的Hmol1-3B细胞的体内致瘤性。将基因表达谱分为两组，并使用281个差异表达基因进行上游调控分析。我们重点关注转录因子，发现 GTN 组中有 33 个转录因子被激活。然后，排除临床样本和细胞系中低表达水平的细胞，选择XBP1进行进一步分析。此外，XBP1下调显着降低绒毛膜癌细胞的迁移和侵袭能力，而XBP1过表达显着增加CHM细胞的迁移和侵袭能力。此外，动物实验表明，XBP1 过表达 Hmol1-3B 小鼠的肿瘤重量和血液人绒毛膜促性腺激素 (hCG) 水平显着高于对照小鼠。RNA-seq 确定 XBP1 是后遗症的关键因素。磨牙 GTN，表明它有助于后磨牙 GTN 的发展。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

A complete hydatidiform mole (CHM) is a common disease and is known to develop post-molar gestational trophoblast neoplasia (GTN). However, the molecular mechanisms underlying the progression of CHM to post-molar GTN remain largely unknown. In this study, we investigated the molecular factors associated with the progression using RNA-seq.We included 13 patients with CHM and performed RNA-seq using freshly frozen samples. We identified differentially expressed genes between patients who developed GTN (GTN group) and those who achieved spontaneous remission after uterine evacuation (SR group), and performed pathway analysis. Then, functional analyses were performed on choriocarcinoma (JAR and JEG-3) and CHM (Hmol1-3B and Hmol1-2C) cells. Moreover, we evaluated the in vivo tumorigenicity of XBP1-overexpressed Hmol1-3B cells.The gene expression profiles were separated into two groups, and an upstream regulator analysis was performed using 281 differentially expressed genes. We focused on transcription factors and identified that 33 transcription factors were activated in the GTN group. Then, excluding those with low expression levels in clinical samples and cell lines, XBP1 was selected for further analysis. Additionally, XBP1 downregulation significantly decreased the migration and invasive abilities of choriocarcinoma cells, whereas XBP1 overexpression significantly increased the migration and invasive abilities of CHM cells. Furthermore, animal experiments showed that tumor weight and blood human chorionic gonadotropin (hCG) levels were significantly higher in the XBP1-overexpressing Hmol1-3B-bearing mice than those in the control mice.RNA-seq identified XBP1 as a key factor in post-molar GTN, suggesting it contributes to the development of post-molar GTN.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.