scholarly journals Integrated Transcriptome and Multiple Activated Pathways in Endometrial Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Jin ◽  
Xiaohua Jiang ◽  
Xin Du ◽  
Weiping Hu ◽  
Shun Bai ◽  
...  

Because the incidence of endometrial cancer is notably increasing worldwide, it has become the leading gynecologic cancer in the United States. Standard treatment results in the loss of reproductive function in women of childbearing age. Furthermore, advanced cancer stages are associated with poor overall survival. The aim of this study was to explore the abnormal expression profile of genes during the development of endometrial cancer, which is essential to provide a better understanding of the mechanisms involved. Five pairs of endometrial cancer tissues and normal endometrial tissues were subjected to next-generation transcriptome sequencing technology. Quantitative real-time PCR (RT-qPCR) was performed to validate the expression profile of key differentially expressed genes (2.0-fold change, adj. p < 0.05) (DEGs) identified in the RNA-seq result. GO and KEGG pathways were used for bioinformatic analyses. The transcriptomic sequencing results showed 1153 DEGs, including 673 upregulated and 480 downregulated genes, in the EC specimens. Decreased expression of ID1, IGF1, GDF7, SMAD9, TGF-beta and WNT4, as well as GDF5, INHBA and ERBB4 overexpression, were confirmed in EC using RT-qPCR. Additionally, EC tissue exhibited marked enrichment in genes promoting cellular adhesion, proliferation, migration and plasma membrane. KEGG analysis revealed changes in various pathways, such as the TGF-beta, PI3K-Akt, Wnt, and estrogen pathways. Our data describe the molecular events involved in the pathogenesis of EC, which may be potential diagnostic markers and targets of therapeutic interventions.

Author(s):  
Penelope M. Webb

The prevalence of overweight and obesity in the United States and elsewhere has increased dramatically in recent decades. It has long been known that obese women have an increased risk of developing endometrial cancer, but recent studies suggest this association is strongest for the most common low-grade endometrioid endometrial cancers and weaker for the other histologic subtypes. There are insufficient data to assess whether obesity affects endometrial cancer-specific survival or whether the relation with all-cause mortality is similar to that seen in the general population. Recent data suggest obesity also increases risk of ovarian cancer, although it may not influence risk of the high-grade serous cancers that account for the majority of ovarian cancer deaths, and that it is also associated with poorer outcomes. There is currently insufficient evidence to draw any clear conclusions regarding the relation between obesity and risk of/survival from other gynecologic cancers although there are suggestions that obesity may increase risk of cervical cancer, particularly adenocarcinoma, and perhaps vulvar cancer. Possible mechanisms whereby obesity might influence gynecologic cancer risk and survival include: its strong association with endogenous estrogen levels among postmenopausal women, its effects on glucose metabolism, its effects on the wide range of adipocytokines and inflammatory mediators that are produced by adipose tissue and altered in concentration among obese individuals, and its potential effects on patient management, particularly with regard to chemotherapy dosing.


2011 ◽  
Vol 21 (2) ◽  
pp. 309-315 ◽  
Author(s):  
Ashley Sinclair Felix ◽  
Faina Linkov ◽  
George Larry Maxwell ◽  
Camille Ragin ◽  
Emanuela Taioli

Introduction:Endometrial cancer (EC) is the most common gynecologic cancer in the United States. Racial disparities in the incidence and mortality of this cancer are apparent; black women are less likely to develop this malignancy and yet are more likely to die when diagnosed. Racial differences of second primary cancer (SPC) have not been examined, and the goal of this study was to examine these differences.Methods:With the use of the National Cancer Institute's Surveillance, Epidemiology, and End Results database, SPC risk in white patients and black patients with EC was compared to the general population and to women with other primary cancers. Standardized incidence ratios (SIRs) of SPC (overall and by tumor site) with 95% confidence intervals were calculated. Poisson regression was used to estimate the race-specific risk of SPC in EC cases treated with radiotherapy versus nonirradiated cases.Results:The analysis included 11,047 patients with EC diagnosed between 1973 and 2007 that developed an SPC. Overall risk of SPC in white women with EC was significantly lower than that in the general population (SIR = 0.85; 95% CI, 0.84-0.87) but significantly higher in black women with EC (SIR = 1.19; 95% CI, 1.08-1.31). White women with EC treated with radiotherapy were more likely to develop SPC compared with nonirradiated cases (incidence rate ratio [IRR], 1.18; 95% CI, 1.14-1.23).Conclusions:This is the first analysis of race-specific SPC risk in EC cases, and it suggests differences between white women and black women with EC. Although exploratory, these data provide important clues about the etiology of SPC in patients with EC. This analysis also highlights the need for careful monitoring after diagnosis and treatment of EC.


2014 ◽  
Author(s):  
Stephen A Cannistra ◽  
Christina I Herold

This chapter focuses on the three types of gynecologic cancer—epithelial cancer of the ovary, cancer of the uterine cervix, and cancer of the endometrium (uterine cancer)—and reviews their epidemiology, diagnosis, differential diagnosis, surgical features, and staging, as well as their risk factors and clinical features. Also discussed are methods of treatment and the management of relapse. Epithelial ovarian cancer occurs at a mean age of 60 years in the United States and is the most lethal of gynecologic tract tumors. However, a recent trial has demonstrated a survival advantage through the use of intraperitoneal chemotherapy for appropriate patients with optimally debulked ovarian cancer. Invasive cervical cancer is uncommon in developed countries, partly because of the effectiveness of Pap smear screening. Nevertheless, cancer of the uterine cervix is the third most common gynecologic cancer diagnosis and cause of death among gynecologic cancers in the United States. However, for women with early-stage cervical cancer, data from several randomized trials indicate an improvement in response rate and survival through the use of combination platinum-based regimens for platinum-sensitive relapse. Also noted is an improvement in survival using combined-modality chemoradiation in appropriate patients with locally advanced cervical cancer. Endometrial cancer is the most frequent tumor of the gynecologic tract; it is estimated that it occurred in over 46,000 women and caused more than 8,000 deaths in the United States in 2011. Recent data indicate improvement in survival using adjuvant platinum-based chemotherapy in appropriate patients with high-risk endometrial cancer. Tables in this chapter review the common histologic types of epithelial ovarian cancer, selected signs and symptoms of ovarian cancer, the International Federation of Gynecology and Obstetrics (FIGO) staging system for epithelial ovarian cancer, differential diagnosis of a complex cyst detected by transvaginal sonography, selected adverse prognostic factors in epithelial ovarian cancer, common chemotherapy agents used in the treatment of epithelial ovarian cancer, the FIGO surgical staging of endometrial cancer, and postoperative management considerations for patients with uterine cancer. Figures illustrate the four histologic subtypes of epithelial ovarian cancer, the intraoperative appearance of stage III epithelial ovarian cancer, and FIGO staging of cervical cancer. This review contains 6 highly rendered figures, 8 tables, and 150 references.


2014 ◽  
Author(s):  
Stephen A Cannistra ◽  
Christina I Herold

This chapter focuses on the three types of gynecologic cancer—epithelial cancer of the ovary, cancer of the uterine cervix, and cancer of the endometrium (uterine cancer)—and reviews their epidemiology, diagnosis, differential diagnosis, surgical features, and staging, as well as their risk factors and clinical features. Also discussed are methods of treatment and the management of relapse. Epithelial ovarian cancer occurs at a mean age of 60 years in the United States and is the most lethal of gynecologic tract tumors. However, a recent trial has demonstrated a survival advantage through the use of intraperitoneal chemotherapy for appropriate patients with optimally debulked ovarian cancer. Invasive cervical cancer is uncommon in developed countries, partly because of the effectiveness of Pap smear screening. Nevertheless, cancer of the uterine cervix is the third most common gynecologic cancer diagnosis and cause of death among gynecologic cancers in the United States. However, for women with early-stage cervical cancer, data from several randomized trials indicate an improvement in response rate and survival through the use of combination platinum-based regimens for platinum-sensitive relapse. Also noted is an improvement in survival using combined-modality chemoradiation in appropriate patients with locally advanced cervical cancer. Endometrial cancer is the most frequent tumor of the gynecologic tract; it is estimated that it occurred in over 46,000 women and caused more than 8,000 deaths in the United States in 2011. Recent data indicate improvement in survival using adjuvant platinum-based chemotherapy in appropriate patients with high-risk endometrial cancer. Tables in this chapter review the common histologic types of epithelial ovarian cancer, selected signs and symptoms of ovarian cancer, the International Federation of Gynecology and Obstetrics (FIGO) staging system for epithelial ovarian cancer, differential diagnosis of a complex cyst detected by transvaginal sonography, selected adverse prognostic factors in epithelial ovarian cancer, common chemotherapy agents used in the treatment of epithelial ovarian cancer, the FIGO surgical staging of endometrial cancer, and postoperative management considerations for patients with uterine cancer. Figures illustrate the four histologic subtypes of epithelial ovarian cancer, the intraoperative appearance of stage III epithelial ovarian cancer, and FIGO staging of cervical cancer. This review contains 6 highly rendered figures, 8 tables, and 150 references.


2021 ◽  
pp. ijgc-2020-002192
Author(s):  
Serena Cappuccio ◽  
Yanli Li ◽  
Chao Song ◽  
Emeline Liu ◽  
Gretchen Glaser ◽  
...  

ObjectiveTo evaluate trends in outpatient versus inpatient hysterectomy for endometrial cancer and assess enabling factors, cost and safety.MethodsIn this retrospective cohort study, patients aged 18 years or older who underwent hysterectomy for endometrial cancer between January 2008 and September 2015 were identified in the Premier Healthcare Database. The surgical approach for hysterectomy was classified as open/abdominal, vaginal, laparoscopic or robotic assisted. We described trends in surgical setting, perioperative costs and safety. The impact of patient, provider and hospital characteristics on outpatient migration was assessed using multivariate logistic regression.ResultsWe identified 41 246 patients who met inclusion criteria. During the time period studied, we observed a 41.3% shift from inpatient to outpatient hysterectomy (p<0.0001), an increase in robotic hysterectomy, and a decrease in abdominal hysterectomy. The robotic hysterectomy approach, more recent procedure (year), and mid-sized hospital were factors that enabled outpatient hysterectomies; while abdominal hysterectomy, older age, Medicare insurance, black ethnicity, higher number of comorbidities, and concomitant procedures were associated with an inpatient setting. The shift towards outpatient hysterectomy led to a $2500 savings per case during the study period, in parallel to the increased robotic hysterectomy rates (p<0.001). The post-discharge 30-day readmission and complications rate after outpatient hysterectomy remained stable at around 2%.ConclusionsA significant shift from inpatient to outpatient setting was observed for hysterectomies performed for endometrial cancer over time. Minimally invasive surgery, particularly the robotic approach, facilitated this migration, preserving clinical outcomes and leading to reduction in costs.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christer Borgfeldt ◽  
Erik Holmberg ◽  
Janusz Marcickiewicz ◽  
Karin Stålberg ◽  
Bengt Tholander ◽  
...  

Abstract Background The aim of this study was to analyze overall survival in endometrial cancer patients’ FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy). Methods A population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses. Results In univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18–1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95–1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival. Conclusion The minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.


Author(s):  
Linda Duska ◽  
Armin Shahrokni ◽  
Melanie Powell

Endometrial cancer is the most common gynecologic cancer, and with a median age of 62 at diagnosis, it affects a significant number of older women. With increasing age and obesity rates in the world’s population, there is an anticipated concomitant increase in older women with endometrial cancer. Older women are more likely to die of endometrial cancer compared with younger patients. Reasons for this include more aggressive tumor biology, less favorable clinicopathologic features, and more advanced disease. Other factors, however, such as reluctance to offer surgical treatment to the older patient and increased complications of treatment are likely to be important. Management of endometrial cancer requires multidisciplinary care (surgery, radiation therapy, and systemic therapy). For each treatment, the feasibility (related to technical aspect of the procedure/treatment), side effects and safety (related to older-patient factors), and the overall benefit as it pertains to older women with endometrial cancer should be assessed carefully with a multidisciplinary approach. Despite the importance of these issues, the data are limited to answer these issues with clarity. In this article, we will review each treatment modality for older women with endometrial cancer. We will introduce the components of comprehensive geriatric assessment and their practical implication for older women with cancer in general and older women with endometrial cancer specifically.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 471
Author(s):  
Camila Pimentel ◽  
Casin Le ◽  
Marisel R. Tuttobene ◽  
Tomas Subils ◽  
Jasmine Martinez ◽  
...  

Acinetobacter baumannii is a nosocomial pathogen capable of causing serious infections associated with high rates of morbidity and mortality. Due to its antimicrobial drug resistance profile, A. baumannii is categorized as an urgent priority pathogen by the Centers for Disease Control and Prevention in the United States and a priority group 1 critical microorganism by the World Health Organization. Understanding how A. baumannii adapts to different host environments may provide critical insights into strategically targeting this pathogen with novel antimicrobial and biological therapeutics. Exposure to human fluids was previously shown to alter the gene expression profile of a highly drug-susceptible A. baumannii strain A118 leading to persistence and survival of this pathogen. Herein, we explore the impact of human pleural fluid (HPF) and human serum albumin (HSA) on the gene expression profile of a highly multi-drug-resistant strain of A. baumannii AB5075. Differential expression was observed for ~30 genes, whose products are involved in quorum sensing, quorum quenching, iron acquisition, fatty acid metabolism, biofilm formation, secretion systems, and type IV pilus formation. Phenotypic and further transcriptomic analysis using quantitative RT-PCR confirmed RNA-seq data and demonstrated a distinctive role of HSA as the molecule involved in A. baumannii’s response.


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