Understanding the Role and Clinical Applications of Exosomes in Gynecologic Malignancies: A Review of the Current Literature

Background: Gynecologic malignancies are those which arise in the female reproductive organs of the ovaries, cervix, and uterus. They carry a great deal of morbidity and mortality for patients, largely due to challenges in diagnosis and treatment of these cancers. Although advances in technology and understanding of these diseases have greatly improved diagnosis, treatment, and ultimately survival for patients with gynecologic malignancies over the last few decades, there is still room for improvements in diagnosis and treatment, for which exosomes may be the key. This paper reviews the current knowledge regarding gynecologic tumor derived-exosomal genetic material and proteins, their role in cancer progression, and their potential for advancing the clinical care of patients with gynecologic cancers through novel diagnostics and therapeutics. Literature Review: Ovarian tumor derived exosome specific proteins are reviewed in detail, discussing their role in ovarian cancer metastasis. The key microRNAs in cervical cancer and their implications in future clinical use are discussed. Additionally, uterine cancer-associated fibroblast (CAF)-derived exosomes which may promote endometrial cancer cell migration and invasion through a specific miR-148b are reviewed. The various laboratory techniques and commercial kits for the isolation of exosomes to allow for their clinical utilization are described as well. Conclusion: Exosomes may be the key to solving many unanswered questions, and closing the gaps so as to improve the outcomes of patients with gynecologic cancers around the world. The potential utilization of the current knowledge of exosomes, as they relate to gynecologic cancers, to advance the field and bridge the gaps in diagnostics and therapeutics highlight the promising future of exosomes in gynecologic malignancies.

Gynecologic organ involvement and incidental gynecologic organ neoplasms in female patients with urothelial carcinoma of the bladder undergoing anterior pelvic exenteration in Rajavithi Hospital

Objective: To evaluate the pathological data of the bladder and gynecologic organs obtained from anterior pelvic exenteration and review the incidence of gynecologic organ involvement and primary gynecologic tumor. Materials and Methods: The clinicopathological data of 70 patients who were diagnosed with bladder transitional cell carcinoma and underwent anterior pelvic exenteration in Rajavithi Hospital between January 2008 and October 2020 were analyzed to examine and determine any correlations. Results: Thirteen (18.5%) patients had gynecologic organ involvement. This consisted of 4 cases (5.7%) involving the uterus, 7 (10%) involving the vagina, 2 (2.8%) involving the ovaries, and 10 (14.2%) involving the cervix. Female patients with gynecologic organ invasion were more likely to have a high pathological T stage (p < 0.001), and have pre-operative hydronephrosis (p = 0.002). From multivariate logistic regression, pre-operative hydronephrosis was associated with increased risk of gynecologic organ invasion (odds ratio 9.57; 95% confidence interval, 1.86 - 49.18; p = 0.007). There were 23 (32%) female patients incidentally diagnosed with benign gynecologic tumors, specifically 16 (22%) cases of myoma uteri, 7 (10%) of adenomyosis and 4 (2.8%) with ovarian cysts. No patient was diagnosed as having primary gynecologic malignancy. Conclusions: The incidence of gynecologic organ involvement in female patients who had undergone anterior pelvic exenteration for urothelial carcinoma of the bladder was 18.5%. Pre-operative hydronephrosis was a risk factor associated with increased risk of gynecologic organ involvement. Information from this study may allow better identification of candidates for gynecologic organ sparing surgery.

Machine Learning-Based Gynecologic Tumor Diagnosis and Its Postoperative Incisional Infection Influence Factor Analysis

Various factors influencing postoperative incisional infection in gynecologic tumors were analyzed, and the value of quality nursing intervention was studied. In this study, 74 surgically treated gynecologic tumor patients were randomly selected from within the hospital as the study population and were divided into study and control groups. For this purpose, the whole-group random sampling method is utilized to compare the postoperative incisional infection rates of the two groups, analyze their influencing factors, and develop quality nursing interventions. In this paper, a breast cancer diagnosis prediction model was developed by combining the self-attentive mechanism. The preprocessing work such as data quantification and normalization was performed first which is followed by adding the preprocessed data to the self-attentive mechanism. This model has solved the problem that recurrent neural networks (RNNs) could not extract and calculate the features at the same time. Likewise, it has solved the drawback that the RNN could not consider global features at the same time when extracting the features, and then, the feature matrix extracted by the self-attentive mechanism was added to the adaptive neural network. The adaptive neural network model for breast cancer diagnosis prediction was constructed and, finally, relevant parameters of the adaptive neural network model were adjusted according to different tasks to make the model performance optimal. Experimental results showed that the postoperative incision infection rate of patients in the study group was 2.70%, which was significantly lower than that of 21.62% in the control group ( P < 0.05 ). Likewise, operation time, operation method, hospitalization time, preoperative fever, diabetes mellitus, and anemia were the main influencing factors of postoperative incision infection in women with gynecologic tumors. The time of surgery, surgical method, long hospital stay, preoperative fever, diabetes, and anemia are the main factors that lead to postoperative incisional infection in female gynecologic tumor patients.

Involvement of Rab25 Biomarker in Pathogenesis of Ovarian Cancer

Ovarian tumor is the third leading common gynecologic tumor and the common leading cause of death in gynecological cancers to the entire global and studies suggested that Rab25 is insinuated in the pathological process of ovarian cancer. Despite the availability of biomarkers for ovarian cancer detection, there are no specific markers that enable the early detection of ovarian cancers which open an avenue to Rab25 to be review. A number of genes and proteins have been reported to be involved in the pathogenesis of ovarian cancers. Of them, Ras-related protein 25 (Rab25) is suggested to be linked to increased risk of ovarian cancer development. Rab25, an intracellular transport protein, belongs to the Rab small GTPase family and regulates various aspects of internalized membrane protein recycling and trafficking occurring inside the cells to the cell membrane. It is known to be involved in cell proliferation, and prevents apoptosis and invasion in ovarian cancer. Rab25 is highly found in epithelial cells and the expression of Rab25 proteins has been implicated to be ubiquitous. Upregulation of Rab25 has also been strongly shown to intensify the cancer cell proliferation and to prevent apoptosis in vitro and in vivo .Here in we will review the past and current studies implicating Rab 25 as potential biomarker in ovarian cancer in addition to pathogenesis

Gynecologic tumor board: a radiologist’s guide to vulvar and vaginal malignancies

Primary vulvar and vaginal cancers are rare female genital tract malignancies which are staged using the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging. These cancers account for approximately 2,700 deaths annually in the USA. The most common histologic subtype of both vulvar and vaginal cancers is squamous cell carcinoma, with an increasing role of the human papillomavirus (HPV) in a significant number of these tumors. Lymph node involvement is the hallmark of FIGO stage 3 vulvar cancer while pelvic sidewall involvement is the hallmark of FIGO stage 3 vaginal cancer. Imaging techniques include computed tomography (CT), positron emission tomography (PET)-CT, magnetic resonance imaging (MRI), and PET-MRI. MRI is the imaging modality of choice for preoperative clinical staging of nodal and metastatic involvement while PET-CT is helpful with assessing response to neoadjuvant treatment and for guiding patient management. Determining the pretreatment extent of disease has become more important due to modern tailored operative approaches and use of neoadjuvant chemoradiation therapy to reduce surgical morbidity. Moreover, imaging is used to determine the full extent of disease for radiation planning and for evaluating treatment response. Understanding the relevant anatomy of the vulva and vaginal regions and the associated lymphatic pathways is helpful to recognize the potential routes of spread and to correctly identify the appropriate FIGO stage. The purpose of this article is to review the clinical features, pathology, and current treatment strategies for vulvar and vaginal malignancies and to identify multimodality diagnostic imaging features of these gynecologic cancers, in conjunction with its respective 2009 FIGO staging system guidelines.

Molecular and Cellular Insights into the Development of Uterine Fibroids

Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.

A Novel Defined Risk Signature of the Ferroptosis-Related Genes for Predicting the Prognosis of Ovarian Cancer

Ferroptosis is an iron-dependent, regulated form of cell death, and the process is complex, consisting of a variety of metabolites and biological molecules. Ovarian cancer (OC) is a highly malignant gynecologic tumor with a poor survival rate. However, the predictive role of ferroptosis-related genes in ovarian cancer prognosis remains unknown. In this study, we demonstrated that the 57 ferroptosis-related genes were expressed differently between ovarian cancer and normal ovarian tissue, and based on these genes, all OC cases can be well divided into 2 subgroups by applying consensus clustering. We utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to develop a multigene risk signature from the TCGA cohort and then validated it in an OC cohort from the GEO database. A 5-gene signature was built and reveals a favorable predictive efficacy in both TCGA and GEO cohort (P &lt; 0.001 and P = 0.03). The GO and KEGG analysis revealed that the differentially expressed genes (DEGs) between the low- and high-risk subgroup divided by our risk model were associated with tumor immunity, and lower immune status in the high-risk group was discovered. In conclusion, ferroptosis-related genes are vital factors predicting the prognosis of OC and could be a novel potential treatment target.

EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.