DigitalUM :: Browsing by Subject "Endometrial cancer"

Browsing by Subject "Endometrial cancer"

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Open Access
ACAT2 negatively modulated by FOXA2 suppresses ferroptosis to expedite the aggressive phenotypes of endometrial cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Xiao, Xin; Huang, Tingyun; Chen, Bin; Zhu, Jinshu; Xiao, Qingbang; Bao, Yuxin
Endometrial cancer (EC) remains a prevalent gynecological disease with a continuously rising incidence and fatality rate. Acyl coenzyme A: cholesterol acyltransferase 2 (ACAT2) has been commonly perceived as a tumor promoter in multiple human malignancies. This study was conducted to specify the role and mechanism of ACAT2 in EC, which has not been covered. The expression and prognostic significance of ACAT2 in EC samples were respectively analyzed by the ENCORI and Kaplan-Meier plotter databases. RT-qPCR and western blot examined ACAT2 and forkhead box protein A2 (FOXA2) expression in EC cells. The CCK-8 method, colony formation, and EdU staining assays detected cell proliferation. The cell cycle was detected by flow cytometry analysis. Wound healing and Transwell assays, respectively, estimated cell migration and invasion. The thiobarbituric acid reactive species (TBARS) method and BODIPY 581/591 C11 probe detected lipid peroxidation levels. FerroOrange staining estimated intracellular iron level. Western blot examined the expression of epithelial-mesenchymal transition (EMT) and ferroptosis-associated proteins. The human TFDB database predicted the binding of FOXA2 with the ACAT2 promoter, which was substantiated by ChIP and luciferase reporter assays. As a result, ACAT2 expression was increased in EC tissues and cells and associated with poor survival outcomes in EC patients. ACAT2 deletion might hinder EC cell proliferation, migration, invasion, and EMT while stimulating cell cycle arrest. Moreover, ACAT2 silencing promoted the ferroptosis of EC cells. Also, FOXA2 inactivated the transcription of ACAT2 through binding with the ACAT2 promoter. FOXA2 interference could promote the proliferation, migration, invasion, EMT, cell cycle, and inhibit the ferroptosis of ACAT2-silenced EC cells, which was partially reversed by the ferroptosis activator erastin. Conclusively, ACAT2 transcriptionally inactivated by FOXA2 might contribute to the malignant progression of EC via the inhibition of ferroptosis.
Open Access
Betulinic acid isolated from Betula platyphylla induces apoptosis and reduces the mTOR/PI3K/AKT signaling pathway in endometrial cancer cells
(2026) Ceren Oy; Mücahit Secme; Duygu Gok Yurtseven; Sema Serter Koçoğlu; Gözde Korkusuz Akçal; Biología Celular e Histología
Endometrial cancer is one of the most common gynecological cancers worldwide, and an average of 42,000 women die each year. Chemotherapy, radiotherapy, and surgery are among the treatments available for endometrial cancer. Currently, drugs used for chemotherapy have had limited success in increasing the cure rate. Betulinic acid, a lupane-type triterpene widely found in the plant kingdom, has attracted attention for cancer treatment in recent years due to its ability to inhibit tumor growth and induce cell apoptosis. The aim of this study is to investigate the mTOR pathway-mediated anticancer effects of betulinic acid in human endometrial cancer cells. The effect of betulinic acid on Ishikawa cell viability was determined by the CCK-8 method. Its effect on the expression of genes involved in apoptosis and the mTOR pathway was assessed by real-time PCR. The effect on protein expression in the mTOR pathway was evaluated with immunohistochemistry and western blot, and the effects on apoptosis via Annexin V. Betulinic acid reduced Ishikawa endometrial cancer cell proliferation. Betulinic acid administration caused a significant decrease in Bcl2 (p=0.008) expression and increased caspase-8 (p=0.001) expression in Ishikawa cells. The results of Annexin V supported the idea that betulinic acid administration triggered apoptosis in Ishikawa cells. The mean rate of apoptotic cells in the betulinic acid group was 22±3.23%, while it was 2.31±0.2% in the control group (p=0.02). Betulinic acid caused a significant decrease in the expression of AKT1 (p=0.0001) and a significant increase in the expression of RAPTOR (p=0.00002). Betulinic acid administration also significantly percentage of p-PI3K, p-AKT, and p-mTOR-positive cells in Ishikawa cells was 89.39±5.19%, 74.84%±5.07, and 82.02%±6.14, respectively, in the control group. In the betulinic acid group, these values were 49.12± 19.12% (p=0.002), 44.46±7.39% (p<0.001), and 53.70±8.94% (p<0.001), respectively. This study showed that betulinic acid decreased Ishikawa cell proliferation, triggered apoptosis, and decreased mTOR signaling; thus, betulinic acid may be a potential anticancer agent for the treatment of endometrial cancer. decreased protein expression in the mTOR pathway. The
Open Access
Clinicopathologic and prognostic significance of cyclooxygenase-2 expression in endometrial carcinoma
(Murcia : F. Hernández, 2005) Lambropoulou, M.; Alexiadis, G.; Limberis, V.; Nikolettos, N.; Tripsianis, G.
Backgroud: Endometrial carcinoma is the most common malignancy of the female genital tract in the Western world. COX-2 is highly expressed in endometrial carcinoma, but there is controversy regarding its clinical role and its possible prognostic role. COX-2 expression was determined by immunohistochemistry and was correlated to standard clinicopathologic variables in a series of primary untreated endometrial carcinoma patients. COX-2 as an accurate predictor of the disease was also analyzed. Methods: One-hundred and ten cases of primary untreated endometrial carcinoma hosts who were admitted to the Department of Obstetrics and Gynecology, University General Hospital of Alexandroupolis, were investigated. Immunohistochemistry was performed using rabbit polyclonal antiserum against human COX-2. Results: Twenty-eight patients (25.5%) were scored as COX-2 positive. A statistically significant association was found between COX-2 overexpression and FIGO stage (p=0.010). A positive correlation was also found with histological grade (p=0.019) and myometrial invasion (p=0.026). No significant association was found with histologic type of the tumor (p=0.164). COX-2 positive patients had a significant association with sort survival (p=0.028). Conclusions: COX-2 expression is an independent clinicopathologic factor and an independent prognostic factor in endometrial carcinoma. It could be used to plan treatment modalities for hosts.
Open Access
E2F1-induced upregulation of TROAP contributes to endometrial cancer progression
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wang, Shanshan; Sun, Yidan; Guo, Minjing; Zhu, Ping; Xin, Beibei
Purpose. To investigate the role of Trophinin-associated protein (TROAP) in endometrial cancer (EC) progression and elucidate how the transcription factor E2F transcription factor 1 (E2F1) modulates EC by upregulating TROAP expression. Methods. TROAP expression in EC tissues and cell lines was analyzed using bioinformatics databases, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry. TROAP was knocked down in EC cells to assess its effects on proliferation, migration, invasion, and glycolysis. Potential transcription factors regulating TROAP were identified, and the relationship between E2F1 and TROAP gene regulation was examined using dual luciferase assay. In vivo tumor growth was evaluated using a mouse xenograft model. Results. TROAP was overexpressed in EC tissues and cell lines compared with normal controls. High TROAP expression correlated with poor differentiation, advanced stage, lymph node metastasis, and worse overall survival in EC patients. Knockdown of TROAP inhibited the proliferation, migration, invasion, and glycolytic capacity of EC cells. E2F1 was identified as a transcriptional activator of TROAP. E2F1 over-expression enhanced TROAP expression and promoted EC cell proliferation, migration, and glycolysis in a TROAP-dependent manner. TROAP knockdown suppressed tumor growth in vivo. Conclusion. TROAP is transcriptionally activated by E2F1 and promotes EC progression by enhancing cell proliferation, metastasis, and glycolysis. The E2F1-TROAP axis may serve as a potential therapeutic target for EC treatment.
Open Access
Endometrial epithelial cell organoids as tools for studying the CD39 family of enzymes and for validating enzyme inhibitors
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Rodríguez Martínez, Aitor; Torrejón Escribano, Benjamín; Eritja, Núria; Dorca Arévalo, Jonatan; Gabaldón, Clara; Sévigny, Jean; Matias Guiu, Xavier; Martín Satué, Mireia
Extracellular adenosine triphosphate (ATP) conducts a complex dynamic system of broadly represented cell signaling. Ectonucleotidases are the enzymes with nucleotide hydrolytic ability that regulate ATP levels in physiological and pathological conditions, thus playing a key role in the so-called purinergic signaling. Altered ectonucleotidase expression has been reported in cancer, and the ectonucleoside triphosphate diphosphohydrolase (NTPDase) family of enzymes, with its best-known form NTPDase1 (CD39), is targeted in cancer immunotherapy. The tandem of enzymes CD39-CD73 is responsible for the generation of immuno-suppressive adenosine in the tumor microenvironment, and inhibition strategies are of great interest. Organoids have emerged as very convenient models for the study of tumors since they are three-dimensional cultures that retain many of the features of tissue. The present study aims to contribute to improving the methodology and the molecular tools needed for the study of ecto-nucleotidases in healthy and disease conditions. The study, performed in an endometrial cancer cell model, could be extended to other types of tumors and pathologies in which the purinergic system is involved. We generated organoids from endometrial cancer cells overexpressing NTPDase2 (CD39L1) and NTPDase3 (CD39L3) as fusion proteins with EGFP, and we performed functional assays by adapting in situ cytochemistry protocols. This allowed us to simultaneously detect enzyme activity and protein expression and to demonstrate that organoids can be used to test ectonucleotidase inhibitors—a result that can be used to develop new cancer treatment options
Open Access
Enhanced CD24 expression in endometrial carcinoma and its expression pattern in normal and hyperplastic endometrium
(Murcia : F. Hernández, 2009) Kim, Kyung Hee; Choi, Jong Sun; Choi, Yoon-La; Shin, Young Kee; Lee, Ho-chang; Seong, In Ock; Kim, Bum Kyung; Chae, Seoung Wan; Kim, Seok-Hyung; Kim, Jin Man
CD24 is known to be an important diagnostic and prognostic marker of several major cancers affecting females. We aimed to determine CD24 expression in normal, hyperplastic, and carcinomatous endometrium and its correlation with estrogen and progesterone receptor expression. A total of 271 cases including 62 normal/atrophic endometrium cases (47/15), 127 endometrial hyperplasia cases (51/52/24, simple/complex/atypical hyperplasia), and 82 endometrial carcinoma cases were immunohistochemically analyzed by using anti-CD24, ER, and PR antibodies that were embedded on paraffin blocks. Next, we assessed the CD24 mRNA expression in these tissues by using RT-PCR. In the normal endometrium, cyclic expression of membranous CD24 was detected during the regular menstrual cycle, i.e., down-regulation in the proliferative phase and up-regulation in the secretory phase. CD24 expression was very infrequent and weak in the atrophic endometrium. In hyperplasias and carcinomas, the expression of both membranous and cytoplasmic CD24 was found to be sharply reduced in the hyperplastic lesions and significantly enhanced in the carcinomas. In the case of carcinomas, high CD24 expression showed significant correlation with high-grade (G2 and 3) (P<0.05). In addition, an inverse correlation was apparent between CD24 and the estrogen and progesterone receptor expressions in normal and diseased endometrium. In conclusion, we demonstrated that CD24 was expressed in a cyclic pattern in the normal endometrium, and its expression was enhanced in case of endometrial carcinoma. These results suggest that CD24 may be involved in tumor progression and can be a useful diagnostic biomarker.
Open Access
Expression and clinical significance of RHCG in endometrial cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Wang, Huifang; Jin, Haihong; Zhao, Sufen
Endometrial cancer (EC) is the most common gynecological cancer. Rhesus family, C glycoprotein (RHCG) has been evidenced to be involved in the occurrence and development of various tumors. This study aimed to investigate the expression and clinical significance of RHCG in EC. Bioinformatics analysis was based on the RNAseq counts data from TCGA database, and the prognosis analysis was performed using the Kaplan-Meier method; 4 cases of endometrioid adenocarcinomas samples and 4 cases of normal proliferative endometrium were collected for qPCR and western blot; immunohistochemistry analysis was employed to assess the expression of RHCG in a tissue microarray; the correlation between RHCG and clinicopathological factors was analyzed through Mann-Whitney U test. The lentiviral interference vector was further constructed. The results demonstrated that RHCG was highly expressed in EC tissues, and RHCG was an independent factor affecting the overall survival of patients. Additionally, the expression of RHCG was related to FIGO stage and tumor infiltrate. After interfering with shRHCG, the proliferation activity of EC cells decreased, the migration ability of cells decreased, the apoptosis of cells increased, and the tumor outgrowth was arrested. In summary, RHCG promotes the malignant proliferation and migration of EC, and makes the cells have anti-apoptotic activity. Our study provides a theoretical basis for RHCG to become a potential therapeutic target for EC in the future
Open Access
Hypoxia-induced Factor-1α in endometrial carcinoma: a mini-review of current evidence
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Dousias, Vassilis; Vrekoussis, Thomas; Navrozoglou, Iordanis; Paschopoulos, Minas; Stefos, Theodore; Makrigiannakis, Antonis; Jeschke, Udo
Despite the well-established role of hypoxia in cancer biology, the literature on its effects on endometrial cancer is scarce; it mainly refers to experimental settings rather than patient-derived results. Herein, an overview of the hypoxia inducible factor 1α (HIF-1α) biology, focusing on endometrial cancer, is presented. The molecular mechanisms possibly involved in endometrial cancer progression are presented, followed by a systematic approach to the current literature on immunohistochemistry evaluation of HIF-1α expression in endometrial carcinoma. Since no consensus has been made regarding HIF-1α evaluation, the evidence of possible involvement of HIF-1α in endometrial carcinoma prognosis is weak. After a consensus has been made, properly powered studies may be able to clarify whether HIF-1α can act as a prognosticator in endometrial carcinoma.
Open Access
Incidence and trend of type I and II endometrial cancer in women from two population-based european cancer registries (1998–2012)
(MDPI, 2022-03-23) Rodríguez-Palacios, Daniel Ángel; Colorado-Yohar, Sandra M.; Velten, Michel; Vaamonde-Martín, Ricardo J.; Ballesta Ruiz, Mónica; Chirlaque López, María Dolores; Ciencias Sociosanitarias; Facultad de Enfermería
Endometrial cancer (EC) is the most frequent female genital tract cancer in Europe. This cohort study aimed to determine age-standardised incidence rates and long-term trends of type I and II endometrial cancer in women from population-based cancer registries in the Region of Murcia (Spain) and the Bas-Rhin area (France). Data of new cases of endometrial cancer between 1998 and 2012 were obtained from the Murcia and Bas-Rhin cancer registries. In that period, 3756 cases of endometrial cancer were recorded, with 3270 corresponding to type I EC and 486 corresponding to type II EC. The Bas-Rhin area presented higher age-adjusted incidence rates than those in the Region of Murcia for both type I EC (24.2 and 19.3 cases/100,000 person-years (py), respectively) and type II EC (4.4 and 2.3 cases/100,000 py, respectively). Joinpoint regression showed no changes in trends. In both populations, there was an increasing trend for both EC types, but the trend was steeper in the Region of Murcia and larger overall for type II EC. Finally, a significant increase was observed in the annual trend of type II EC. Further studies are warranted to determine the potential risk factors, and continued efforts are needed to improve the recording and monitoring of EC types.
Open Access
Inhibin beta B: a useful tumor marker in uterine endometrioid adenocarcinomas?
(F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Mylonas, Ioannis
Inhibins, dimeric peptide hormones composed of an alpha-subunit and one of two possible beta-subunits (betaA or betaB), exhibit substantial roles in human reproduction and in endocrine-responsive tumours. However, the prognostic significance and clinical implications of the inhibin-betaB subunit in uterine endometrioid adenocarcinomas is still not defined yet. A series of 227 uterine endometrioid adenocarcinomas of a previous well-characterized cohort were re-evaluated for the expression of the inhibin-betaB subunit and correlated with several clinicopathological characteristics and the clinical outcome. In this re-analysis, the betaB-subunit expression demonstrated a significant association with the patients' age and cervical involvement. However, inhibin-betaB did not significantly affect the patients survival in this large cohort group. However, patients with a higher intensity of betaB-subunit immunolabelling had a slightly worse survival expectation, although without any significant association, suggesting that this subunit might have a substantial role in the carcinogenesis and pathology of endometrioid adenocarcinomas. Thus, the inhibin-betaB subunit appears not to be a useful prognostic marker regarding endometrioid adenocarcinomas. However, further research is warranted in elucidating the possible implications of inhibin-ßB and endometrial carcinogenesis.
Open Access
KIF22 promotes the proliferation and immune escape of endometrial cancer cells by activating the STAT3/PDL1 pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Chaohe Zhang; Chaoqun Wang; Biología Celular e Histología
Objective. Endometrial cancer (EC) is a common gynecologic malignancy with high morbidity and mortality. Kinesin Family member 22 (KIF22) is regarded as a critical oncogene, but its functions in EC progression remained elusive. Hence, this research elucidated the role of KIF22 in EC development and studied the possible mechanism. Methods. KIF22 expression in EC and the relationship with the overall survival of EC cases were determined by GEPIA and online K-M plotter. After transfection with sh-KIF22, cell viability and invasion were evaluated utilizing CCK-8 and Transwell assays. The content of IFN-γ, IL-2, and TNF-α was assessed utilizing an ELISA assay. The protein levels of p-STAT3, STAT3, and PD-L1 were examined using western blot. A xenograft tumor was constructed to assess tumor growth. Results. KIF22 was elevated in EC, with high KIF22 levels presenting poor overall survival. Additionally, silenced KIF22 restrained EC cell viability, invasion ability, and STAT3/PD-L1 pathway, enhanced the viability of CD8+ T cells, and elevated the levels of IFN-γ, IL-2, and TNF-α. Moreover, the rescue assay revealed that STAT3 overexpression counteracted the inhibitory effect of silenced KIF22 on EC cell proliferation, invasion and immune escape. Furthermore, silenced KIF22 repressed EC tumor growth and p-STAT3 and PD-L1 levels, and elevated the IFN-γ level in vivo. Conclusion. The findings demonstrated that KIF22 was elevated in EC and correlated with a poor prognosis. Silenced KIF22 repressed cell proliferation, invasion, and immune escape via suppressing the STAT3/PD-L1 pathway in EC.
Open Access
Mechanism of PTPN18 for regulating the migration and invasion of endometrial cancer cells via the MYC/PI3K/AKT pathway
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Suo, Shiqi; Chen, Song; Zhou, Liyuan; Xu, Ruili; Li, Jingxia; Li, Wei
Objective. Endometrial cancer (EC) is a prevalent gynecologic malignancy. The critical role of PTPN18 in EC has been reported, while its role in the aerobic glycolysis of EC cells remains unclear. Our current study focused on the mechanism of PTPN18 in the regulation of aerobic glycolysis in EC. Methods. PTPN18 expression levels in endometrial stromal cells (KC02-44D) and EC cells (KLE, HEC-1-A, HEC-1B, and HEC-50) were determined. Following transfection of sh-PTPN18 in HEC-1-A cells, the changes in cell migratory and invasive abilities were assessed by the Transwell assay, and the changes in glucose consumption, lactic acid secretion, and ATP levels were detected using kits. The expression levels of glycolysis-related proteins HIF-1α, PKM2, and LDHA and the activation of the MYC/PI3K/AKT pathway were detected by Western blot. Additionally, sh-PTPN18 and pcDNA3.1-MYC were transfected into HEC-1-A cells to further explore their roles in the changes in aerobic glycolysis, migration, and invasion ability of EC cells. Results. Expression of PTPN18 in EC cells was up-regulated (HEC-1-A>HEC-1B>HEC-50>KLE). PTPN18 knockdown suppressed EC cell migration and invasion. Additionally, PTPN18 knockdown reduced glucose consumption, lactate production, ATP levels, and glycolysis-related protein levels (HIF-1α, PKM2, LDHA). PTPN18 knockdown inhibited the activation of the MYC/PI3K/AKT pathway in EC cells. MYC overexpression partially annulled the inhibitory effects of PTPN18 knockdown on aerobic glycolysis, migration, and invasion of EC cells. Conclusion. Our present study provided evidence that the knockdown of PTPN18 inhibited the aerobic glycolysis, migration, and invasion of EC cells by suppressing the MYC/PI3K/AKT pathway
Open Access
Micro-RNA signature of lymphovascular space involvement in type 1 endometrial cancer
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2017) Canlorbe, Geoffroy; Castela, Mathieu; Bendifallah, Sofiane; Wang, Zhe; Lefevre, Marine; Chabbert Buffet, Nathalie; Aractingi, Selim; Daraï, Emile; Méhats, Céline; Ballester, Marcos
Objective. Lymphovascular space involvement (LVSI) is a major prognostic factor in type 1 endometrial cancer (EC). However, its use has been criticized because of poor subjectivity. MicroRNA signatures have recently been linked to EC pathologic characteristics. The aim of this study was to evaluate whether microRNA profiles of type 1 EC can be related to LVSI status and used as a tool to adapt therapy. Study Design. MicroRNA expression was assessed by chip analysis and qRT-PCR in 12 formalin-fixed paraffin-embedded grade 2 EC specimens with positive LVSI and in 12 specimens with negative LVSI. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. Results. The expression levels of microRNAs 34c5p, -23b-5p, and 23c were significantly lower in the EC with positive LVSI compared to those with negative LVSI. Women with a microRNA-34c-5p fold change <0.15 were more likely to have positive LVSI status (92.3%) compared with those with a microRNA-34c-5p fold change >0.15 (0.0%), p<0.001. Furthermore, women with a microRNA-23b-5p fold change <0.51 were more likely to have positive LVSI status (90.0%) compared with those with a microRNA-23b-5p fold change >0.51 (21.4%), p=0.003. Conclusion. This was the first study to investigate the relative expression of microRNA in type 1 EC according to LVSI status. This microRNA expression profile may provide a basis for further study of the microRNA function in EC, and be used as a diagnostic tool for LVSI status.
Open Access
MiR-196a-5p facilitates progression of estrogen-dependent endometrial cancer by regulating FOXO1
(Universidad de Murcia, Servicio de Publicaciones, 2023) Zhu, Yuzhang; Tang, Yanfei; Fan, Yaohua; Wu, Dongjuan
Background and Purpose. Estrogen-dependent endometrial cancer mainly occurs in younger pre-menopausal and post-menopausal women and threatens their health. Recently, microRNAs (miRNAs) have been considered as novel targets in endometrial cancer treatment. Therefore, we aimed to explore the effect of miRNA (miR)-196a-5p in estrogen-dependent endometrial cancer. Methods. 17β-estradiol (E2; 2.5, 5, 10 and 20 nM) was used to treat RL95-2, HEC-1B and ECC-1 cells followed by cell viability assessment using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The level of miR-196a-5p was measured by reverse transcription-quantitative PCR (RT-qPCR). We then transfected miR-196a-5p mimic/inhibitor and Forkhead box protein O1 (FOXO1) small interfering RNA (siRNA) into E2-treated cells. Apoptotic cells were measured by flow cytometry. Wound healing and Transwell assays were implemented to assess migration and invasion. Bioinformatics and luciferase reporter assays were applied to confirm the interaction between miR-196a-5p and FOXO1. Immunoblotting determined the levels of FOXO1, Bcl-2, Bax, Caspase 3. Results. E2 promoted cell viability and miR-196a-5p expression in RL95-2 and ECC-1 cells. miR-196a-5p mimic enhanced cell viability, migration and invasion but suppressed apoptosis and FOXO1, whilst miR-196a-5p inhibitor blocked these processes. In addition, miR-196a-5p upregulated Bcl-2, but down regulated Bax and Caspase 3 expression, an effect that was reversed by miR-196a-5p inhibitor. We determined that miR-196a-5p targeted FOXO1, and that si-FOXO1 blocked the effects of miR-196a-5p inhibitor on viability, apoptosis, migration and invasion of E2-treated RL95-2 and ECC-1 cells. Conclusions. Our findings suggested potential diagnostic and therapeutic applications for miR-196a-5p and its FOXO1 target in patients suffering from estrogen-dependent endometrial cancer.
Open Access
Prognostic significance of BAF57 expression in patients with endometrial carcinoma
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Kagami, S.; Kurita, T.; Kawagoe, T.; Toki, N.; Matsuura, Y.; Hachisuga, T.; Matsuyama, A.; Hashimoto, H.; Izumi, H.; Kohno, K.
This study was conducted to elucidate the prognostic significance of BAF57 in patients with endometrial carcinoma. We investigated the relationship between the immunohistochemical expression of BAF57 and various clinicopathological variables in 111 endometrial carcinomas. Both univariate and multivariate regression analyses were performed. The correlations between the BAF57 expression and the other variables including estrogen receptor (ER) and p53 were examined. The high nuclear BAF57 expression was detected in 42 (37.8%) endometrial carcinomas, and 69 (62.2%) endometrial carcinomas were defined as having low nuclear BAF57 expression. The BAF57 expression was significantly associated with the surgical stage, grade of the tumor, myometrial invasion, lympho-vascular space invasion (LVSI) and lymph node metastasis. The 10-year overall survival rates of patients with low and high BAF57 expression were 96.9% and 58.2%, respectively (p<0.001). A multivariate analysis identified BAF57 expression as an independent prognostic factor. The BAF57 expression was significantly correlated with p53 expression (r=0.312, P=0.001), but was not correlated with ER expression (r= -0.141, P=0.14). The high BAF57 expression is an independent marker of poor prognosis of the patients in endometrial carcinomas. The inhibition of BAF57 activity may be one of the candidates for endometrial cancer therapy, especially therapy for aggressive tumors showing overexpression of p53
Open Access
Role of INPP4B in the proliferation, migration, invasion, and survival of human endometrial cancer cells
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zhao, Jing; Du, Xue-mei; Si, Wen; Zhao, Xian-he; Zhou, Zi-qi
Background. Inositol polyphosphate 4-phosphatase type II (INPP4B) has been identified as a tumor repressor in several human cancers while its role in endometrial cancer has not been investigated yet. Therefore, the current study was designed to determine whether INPP4B participates in the progression of endometrial cancer by utilizing clinical data and experimental determination. Materials and methods. We first include six chemotherapy-treated patients with recurrent and metastatic endometrioid carcinoma to determine the relationship between INPP4B mutation and relative tumor burden. By using siRNA-mediated gene silencing and vector-mediated gene overexpression, we further determined the effect of manipulating INPP4B expression on the proliferation, invasion, and survival of endometrial cancer cells. Furthermore, the repressing effect of INPP4B together with its role in chemotherapy was further validated by xenograft tumor-bearing mice models. Western blot analysis was used to explore further downstream signaling modulated by INPP4B expression manipulation. Results. Two of the patients were found to have INPP4B mutations and the mutation frequency of INPP4B increased during the progression of chemotherapy resistance. Endometrial cancer cells with silenced INPP4B expression were found to have promoted tumor cell proliferation, invasion, and survival. Endometrial cancer cells overexpressing INPP4B were found to have decreased tumor cell proliferation, invasion, and survival. An in vivo study using six xenograft tumor-bearing mice in each group revealed that INPP4B overexpression could suppress tumor progression and enhance chemosensitivity. Furthermore, INPP4B overexpression was found to modulate the activation of Wnt3a signaling. Conclusion. The current study suggested that INPP4B could be a suppressor in endometrial cancer progression and might be a target for endometrial cancer treatment. Also, INPP4B might serve as a predictor of chemosensitivity determination
Open Access
Role of miRNAs in endometrial cancer
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Li, Shuangdi; Zhang, Jiarong; Wan, Xiaoping
Endometrial cancer (EC) is the most common gynecologic malignancy. MicroRNAs (miRNAs) were recently associated with carcinogenesis and progression of EC. In this review, we discuss recent advances and the emerging role of miRNAs in EC and their clinical implications, with special emphasis on the differences between deregulated miRNAs in type I and type II EC, as well as the impact of this dysregulation on EC initiation and progression.
Open Access
The expression of MMP-14 and microRNA-410 in FFPE tissues of human endometrial adenocarcinoma
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Rak, Beata; Garbicz, Filip; Paskal, Wiktor; Pełka, Kacper; Marczewska, Janina Maja; Wołosz, Dominika; Włodarski, Paweł
Endometrial cancer (EC) is the most common gynecological malignancy in Europe and North America. It is classified into two types exhibiting different characteristics and prognosis. Type I is an estrogen-dependent tumor, histologically classified as low grade and low stage, usually with an excellent prognosis. Type II EC is unrelated to estrogen stimulation and is characterized by a poor prognosis. MicroRNAs (miRNAs, miRs) are small non-coding RNA polynucleotides that regulate gene expression posttranscriptionally. Various dysregulations in microRNA expression are often considered to have an impact on the diagnosis, prognosis and overall survival in patients diagnosed with different types of cancers. Recent data suggest that microRNAs play an important role in the pathogenesis of EC. The aim of the study was to evaluate the involvement of matrix metaloprotease 14 (MMP-14) and microRNA-410 in formation of the EC tumor. To this end expression of MMP-14 and microRNA-410 was assessed within the cancer, transient and healthy zones in the histological sections of tumours using immunohistochemical staining and laser capture microdissection (LCM) followed by a quantitative real-time PCR. The results revealed significantly higher expression of MMP14 in the cancer tissue zone in comparison to the healthy tissue zone, as well as a lower expression of microRNA410 in the cancer zone compared with the healthy zone. This reverse correlation may suggest a regulatory role of miRNA-410 in modulating levels of MMP-14 in EC. This is the first report on such regulation in human endometrial cancer.
Open Access
The incidence and clinical significance of lymph node micrometastases determined by immunohistochemical staining in stage I - lymph node negative endometrial cancer
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) McCoy, Amy; Finan, Michael A.; Boudreaux, F.T.; Tucker, J. Alan; Lazarchick, John J.; Donnell, Robert M.; Rocconi, Rodney P.
Objective: Determine the incidence and clinical relevance of lymph node micrometastases found with immunohistochemical (IHC) staining in patients diagnosed with stage I lymph node-negative endometrial adenocarcinoma. Methods: Eligible patients with endometrioid-type histology and negative lymph nodes by H&E were identified by a computerized database. After histologic confirmation, all paraffin-embedded pathologic specimens were freshly sliced and stained with IHC stains for pancytokeratin. Slides were interpreted by two pathologists and positive IHC staining for micrometastases was defined as positive staining of cells <2 mm in greatest dimension. Patient demographics, clinicopathologic factors, and follow-up data were abstracted. Results: Fifty-one patients were included in our study. Most patients had stage IA (84%) tumors of grade 2/3 histology (51%), and 11 patients (22%) received adjuvant therapy. Mean number of lymph nodes was 12.2 per patient. Of 151 lymph node paraffin blocks evaluated for pancytokeratin, only two (1.3%) had IHC-positive micrometastases. The two lymph node-positive results occurred in separate patients, leading to 3.9% of all patients in our cohort. Both micrometastatic lymph node-positive patients had adjuvant radiation therapy for uterine high-risk factors and are currently without evidence of disease at 15 and 16 months, respectively. Three lymph node-negative patients (6.1%) have developed recurrences within a median follow-up of 15 months. Conclusion: The incidence of IHC stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged endometrial cancer and does not justify routine IHC staining. Additionally, as little evidence exists to support the clinical significance of IHC-stained micrometastases in endometrial cancer, further study is warranted
Open Access
The usefulness of p16 and COX-2 expression on the prediction of progression to endometrial cancer
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Kalkan, Hande Ece; Akman, Levent; Serin, Gurdeniz; Terek, Mustafa Cosan; Zekioglu, Osman; Ozsaran, Ahmet Aydin
Objectives. Endometrial cancer (EC) is the most commonly diagnosed gynecological cancer. Endometrial hyperplasia (EH) is a more common diagnosis than EC. Endometrial hyperplasia is found in approximately 1.5% of all women presenting with abnormal bleeding. Endometrial hyperplasia progresses to EC, and especially, cancer risk increases in cases with atypical hyperplasia. p16, one of the tumor suppressor proteins involved in the cell cycle, and COX-2, one of the key enzymes of prostaglandin synthesis, are important markers for the diagnosis of both EH and EC. There is lack of consensus in the classification, diagnosis and treatment of EH. The subject of changes in the cell cycle in the progression of endometrial pathologies may help to identify and prevent these affected pathways in the treatment stage. The aim of this study is to investigate the expression of p16 and COX-2 during the development of EC from EH. Material and methods. We investigated COX-2 and P16 expressions in patients with proliferative endometrium, complex/simple endometrial hyperplasia and endometrioid adenocarcinoma. Results. p16 expression increased in EH and EC (p<0.001). COX-2 expression was increased in endometrial cancer compared to other groups, but this increase was not found to be statistically significant. Although p16 and COX-2 expression were increased in patients with advanced grade/stage, lymphovascular invasion, and >50% of myometrial invasion, this increase was not statistically significant. Conclusions. More detailed studies are needed to investigate the prognostic significance of the COX-2 molecule. COX-2 might be a potential biomarker for the prognosis of endometrial cancer and a potential therapeutic target for EC treatment. Also, it might be used to prevent the progression of precursor lesions to invasive EC.