Project description:Endometrioid endometrial carcinoma (EEC), an estradiol-related disease, remains a serious health threat to women because of its high incidence and trend of rejuvenation. Accumulating evidence has highlighted that microRNAs (miRNAs) and messenger RNAs (mRNAs) play important roles in various biological processes involved in the pathogenesis of EEC. This study aimed to identify the potential prognostic biomarkers associated with EEC regulated by estradiol.
Project description:The molecular events that mediate the epithelial to mesenchymal transition (EMT) in endometrial cancer remain poorly understood. Using cDNA microarrays, we analyzed a group of endometrial carcinosarcomas (ECS), a true example of EMT in vivo, and we compared their gene expression profiles with those obtained from a group of endometrioid endometrial carcinomas (EEC). The HMGA2 gene (High Mobility Group AT-hook 2), an embryonic nuclear factor that mediates EMT in various tumour models, was among the genes overexpressed in ECS, and HMGA2 overexpression was confirmed in 54% of ECSs by qRT-PCR and immunohistochemistry. Moreover, we found a significant inverse correlation between the expression of HMGA2 and let-7b, a member of the let-7 family of miRNAs that represses HMGA2 expression. These changes were also associated with overexpression of Lin28B, a suppressor of microRNA biogenesis implicated in cancer progression and metastasis. Finally, HMGA2 overexpression, which was detected in less than 3% of EECs, was observed in many non-endometrioid carcinomas (46%). For the first time, we describe a role for HMGA2 in both the process of EMT that contributes to endometrial carcinogenesis and in the acquisition of aggressive phenotypes by this neoplasia. Moreover, we demonstrate changes in the expression of genes modulating processes such as EMT, muscle differentiation, the expression of cancer testis antigens (CTAs) and the immune response. Identification of new molecular markers in endometrial carcinogenesis 15 endometrial carcinosarcomas and 23 endometrioid endometrial carcinoma
Project description:To establish predictive models based on molecular profiles of endometrial lesions that might help to identify progestin insensitive endometrial atypical hyperplasia (EAH) or endometrioid endometrial cancer (EEC) patients before progestin-based fertility preserving treatment. Endometrial lesions from progestin sensitive or progestin insensitive patients were prospectively collected before progestin treatment and analyzed by ATAC-Seq and RNA-Seq. Potential chromatin accessibility and expression profile were compared between PS and PIS groups. Candidate genes were identified by bioinformatic analysis and literature review. Expanded samples (n = 35) were used for verification and model construction.
Project description:Objectives: The aim of this study was to identify the dysregulated genes involved in tumorigenesis, invasion, and metastasis of endometrial endometrioid adenocarcinoma (EEC). Materials and methods: Surgical specimens of endometrial tissues were obtained from 20 patients with normal endometrium (NEM), 20 patients with atypical endometrial hyperplasia (AEH), and 169 patients with EEC. The expression profiles of NEM, AEH, and EEC were compared by using GeneChip Array. The expression of dysregulated genes was first validated by semi-quantitative reverse transcriptase PCR (SQ RT-PCR). The gene expression levels were determined by real time reverse transcriptase PCR (RTQ RT-PCR) in 85 EEC patients as the training test and 84 EEC patients as the testing test. The protein expressions were then examined by immunohistochemical (IHC) staining. The correlations between the expression of dysregualted genes and clinico-pathologic parameters such as tumorigenesis, invasion, and metastasis of EEC were finally evaluated. Results: Seven dysregulated genes were identified by SQ RT-PCR after microarray analysis. Conclusions: uPA is a dysregulated gene in the tumorigenesis of endometrial carcinomas. The gene expression between tissues from NEM, AEH, and EEC were analyzed by microarray. The samples were grouped according to clinical stages but selected at random from our list of banked, frozen tissues. Ten NEM, 10 AEH, and 20 EEC of early and advanced stages were used for microarray experiments (Group 1: early-staged (stages I and II) EEC (n=10), Group 2: advanced-staged EEC (stages III and IV) (n=10)). Samples were pooled in equimolar amounts (10 samples / pool) for microarray analysis.
Project description:To establish predictive models based on molecular profiles of endometrial lesions that might help to identify progestin insensitive endometrial atypical hyperplasia (EAH) or endometrioid endometrial cancer (EEC) patients before progestin-based fertility preserving treatment. Endometrial lesions from progestin sensitive or progestin insensitive patients were prospectively collected before progestin treatment and analyzed by ATAC-Seq and RNA-Seq. Potential chromatin accessibility and expression profile were compared between PS and PIS groups. Candidate genes were identified by bioinformatic analysis and literature review. Expanded samples (n = 35) were used for verification and model construction.
Project description:Objectives: The aim of this study was to identify the dysregulated genes involved in tumorigenesis, invasion, and metastasis of endometrial endometrioid adenocarcinoma (EEC). Materials and methods: Surgical specimens of endometrial tissues were obtained from 20 patients with normal endometrium (NEM), 20 patients with atypical endometrial hyperplasia (AEH), and 169 patients with EEC. The expression profiles of NEM, AEH, and EEC were compared by using GeneChip Array. The expression of dysregulated genes was first validated by semi-quantitative reverse transcriptase PCR (SQ RT-PCR). The gene expression levels were determined by real time reverse transcriptase PCR (RTQ RT-PCR) in 85 EEC patients as the training test and 84 EEC patients as the testing test. The protein expressions were then examined by immunohistochemical (IHC) staining. The correlations between the expression of dysregualted genes and clinico-pathologic parameters such as tumorigenesis, invasion, and metastasis of EEC were finally evaluated. Results: Seven dysregulated genes were identified by SQ RT-PCR after microarray analysis. Conclusions: uPA is a dysregulated gene in the tumorigenesis of endometrial carcinomas.
Project description:Accurate methods to predict nodal and distant metastasis are needed in endometrioid endometrial cancer (EEC) patients to advance personalized care and reduce both overtreatment and undertreatment. A transcript-based classifier for predicting risk of nodal and distant metastasis in EEC patients was developed, and shown to outperform a panel of clinical and molecular features We used microarrays to detail the gene expression in EEC patients and identified a classifer to predict nodal and distant metastasis
Project description:We examined the mechanism by which adiposity regulates endometrioid endometrial cancer progression. Ishikawa EEC cells were co-cultured with mature adipocytes in presence or absence of SIRT1 inhibitor EX527, and total RNA was isolated for RNA-seq analysis and focus on the functional relevance that adipocyte co-culture affected pathways and related biomarkers may have in endometrial cancer response to adiposity.
