Cancer Of Female Reproductive System Research Articles

Reproductive system cancer in females of the Tyva Republic. Epidemiological characteristics

Background. The incidence of female reproductive system cancer, including breast, cervical, ovarian and uterine cancers, is steadily increasing, and therefore it is advisable to conduct an epidemiological analysis and assess the quality of medical care. The purpose of the study was to analyze the epidemiological characteristics of reproductive system cancer in females of the Tyva Republic. Material and Methods. The reporting forms № 7 “Cancer incidence in the Tyva Republic” for 2013–2022 were used. Age-standardized incidence rates were calculated using the “Oncostat” program, and cancer care quality was assessed using “Cancer Care Indicators” program. Results. Reproductive system cancer in the Tyva Republic accounted for 46.3 % of all malignant neoplasms in females during 2013–2022. In 2022, breast cancer was the most common cancer (16.2 %) followed by cervical cancer (13.7 %), ovarian cancer (6.7 %), and uterine cancer (4.0 %). During the study period, none of these cancers showed a statistically significant increase in agestandardized incidence rates (AS R). In 2022, age-standardized incidence rates in the Tyva Republic were higher than those in the Siberian Federal District for cervical cancer (27.5 ± 3.7 vs 16.3 ± 0.4 0/0000) and for ovarian cancer (14.1 ± 2.8 vs 12.7 ± 0.3 0/0000), but lower for breast cancer (32.4 ± 4.1 vs 58.7 ± 0.6 0/0000) and uterine cancer (8.6 ± 2.2 vs 19.7 ± 0.4 0/0000). Overall, cancer care quality indicators for reproductive system cancers had improved. Active detection increased from 22.0 to 29.8 %, p=0.039 (in the Siberian Federal District: from 27.6 to 37.2 %, p=0.001). The detection rate at I–II stages increased from 53.7 to 75.2 %, p=0.004 (in the Siberian Federal District: from 63.0 to 71.3 %, p=0.001). The percentage of advanced stages decreased from 37.4 % to 15.5 %, p=0.001 (from 27.4 % to 23.1 % in the Siberian Federal District, p=0.013). The oneyear mortality rates also decreased from 19.0 to 5.4 %, p=0.013 (in the Siberian Federal District: from 11.8 to 8.5 %, р<0.001). The high incidence of cervical cancer, the absence of noticeable optimal changes in the early detection and the high prevalence of HPV infection among the female population of the Tyva Republic indicate the relevance of mass HPV testing as a part of secondary cancer prevention. Conclusion. The high incidence of female reproductive system cancer and the current status of reproductive cancer care in the Republic of Tyva dictate the need to strengthen primary, secondary and tertiary cancer prevention.

Predominant localization and ways of metastatic dissemination to the brain of malignant tumors of the female reproductive system

Background. Metastases of the female reproductive system cancer to the brain are rare and reach about 5 % of all cases with metastatic lesions of the central nervous system. The most common metastases are ovarian cancer (0.49–6.1 %), endometrial cancer (0.4–1.2 %) and cervical cancer (0.3–0.9 %). The predominant localization and ways of spreading metastases to the brain in this category of tumors may differ from lung cancer, breast cancer, kidney cancer or melanoma.Aim. To analyze the localization of brain metastases of malignant tumors of the female reproductive system and the ways of dissemination of malignant cells from the primary focus to the central nervous system.Materials and methods. From 2013 to 2020, a total number of 448 patients with metastatic brain tumors from different cancers were operated on at the Department of Neuro‑Oncology of the Federal Center of Neurosurgery (Novosibirsk). Metastases of tumors of the female reproductive system were presented in 32 (7.1 %) cases. The average age was 55.1 (27–72) years. Ovarian cancer was the primary focus in 24 (5.3 %) cases, endometrial cancer – in 6 (1.3 %), cervical cancer – in 2 (0.4 %). Occipital lobe was the most often location for the metastases in the brain and occurred in 10 (31.3 %) patients. Subtentorial localization was on the second place and noted in 9 (28.1 %) cases. Of these, metastases to the cerebellum were registered in 8 cases and in 1 case the metastasis was located in the brain stem.Results. Gross total removal of metastasis was achieved in all 32 patients. Of 9 cases with subtentorial localization of metastasis, only 1 patient had lung metastases verified. Regression of neurological symptoms and improvement of the condition were noted in 16 patients after surgery. The Karnovsky performance score at the time of discharge was 85.2.Conclusion. The subtentorial location of metastases in malignant tumors of the female reproductive system occupies one of the leading places. This is because the dissemination of tumor cells from the pelvis can occur through a Batson vertebral venous system directly to the cerebellum or brain stem without the pulmonary blood circulation and lung dissemination. This should be taken into account for the early diagnosis of subtentorial metastatic brain tumors and referral of these patients for neurosurgical treatment.

Exposure to di-2-ethylhexyl phthalate (DEHP) increases the risk of cancer

Cancer is a major socioeconomic burden that seriously affects the life and spirit of patients. However, little is known about the role of environmental toxicant exposure in diseases, especially ubiquitous di-(2-ethylhexyl) phthalate (DEHP) which is one of the most widely used plasticizers. Hence, the objective of this study was to assess the potential association between cancer and DEHP. The data were collected using the 2011–2018 National Health and Nutrition Examination Survey (NHANES) data (n = 6147), and multiple logistic regression was conducted to evaluate the association. The concentrations of DEHP were calculated by each metabolite and split into quartiles for analysis. After adjusting for confounding factors, DEHP was significantly associated with an increased risk of cancer prevalence, and the metabolites of DEHP showed similar results (OR > 1.0, p < 0.05). Simultaneously, the association remained when the analyses were stratified by age and sex, and the risk of cancer appeared to be higher in male patients. In addition, further analysis suggested that DEHP exposure obviously increased the risk of female reproductive system cancer, male reproductive system cancer, and other cancers (OR > 1.0, p < 0.05) but not skin and soft tissue cancer. DEHP exposure is associated with the risk of cancer, especially female reproductive system cancer, male reproductive system cancer and other cancers.

Debate on the oncologic potential of sex steroid preparations

Background. Thanks to numerous worldwide studies, the significant contribution of the hormonal component to the oncological risks of the organs of the female reproductive system is beyond doubt. Of great interest is the analysis of world research on the oncological potential of hormonal drugs, namely COCs and MGT, since this issue continues to be one of the most complex and controversial.&#x0D; Aim. This study aimed to contribution of hormonal factors to the development of cancer of the female reproductive system, namely breast, cervical, endometrial and ovarian cancers.&#x0D; Materials and Methods. The study was conducted on the basis of the Center of Gynecology and Reproductive Technologies of the FSAU “National Medical Research Center “Treatment and Rehabilitation Center” of the Ministry of Health of the Russian Federation, the Department of Oncogynecology of the University Clinical Hospital No. 4 of the I.M. Sechenov First Moscow State Medical University. The analysis of medical documentation for the period from January 2015 to December 2021 was carried out. The study included 1842 patients with verified oncological disease of the female reproductive system, who had a history of taking hormonal drugs of the following pharmacological groups: hormonal contraceptives, menopausal hormone therapy drugs. The age of all patients ranged from 26 to 83 years (mean age 51.98±10.3 years). The control group consisted of 611 patients without oncological diseases, who have a history of indications for taking hormonal drugs of these pharmacological groups.&#x0D; Results. When assessing the effect of the duration of MGT intake on the risk of developing breast cancer, it was found that MGT intake for a total of more than 6 years was associated with a higher risk of developing breast cancer (HR 1.18; CI 1.02–1.36; p 0.001). Using the Wald method, we found that the probability of developing breast cancer is associated with a BMI of more than 25 kg/m2 and long-term intake of combined MGT for a total of more than 6 years. When assessing the effect of the duration of MGT intake on the risk of developing RTM, it was found that MGT intake for a total of more than 6 years was associated with a higher risk of developing RTM (HR 1,432; CI 1,172–1,750; p 0.001). Using the Wald method, we found that the probability of developing RTM is associated with the presence of a BMI of more than 25 kg/m2, prolonged MGT intake for a total of more than 6 years and the presence of endometrial hyperplastic processes, adenomyosis, hypertension in the anamnesis. When assessing the effect of the duration of COC intake on the risk of developing breast cancer, it was found that taking COC for a total of more than 7 years was associated with a higher risk of developing breast cancer (HR 1.68; CI 1.1–2.5; p=0.010). According to the Wald method, it was revealed that the probability of developing breast cancer is associated with the presence of HPV type 16, a BMI of more than 25 kg/m2 and prolonged intake of COCs for a total of more than 7 years. When assessing the effect of the duration of MGT intake on the risk of developing PC, it was found that MGT intake for a total of more than 9 years was associated with a higher risk of developing PC (HR 1.65; CI 1.2–2.3; p=0.010). Using the Wald method, we found that the probability of developing RYA is associated with the presence of a BMI of more than 25 kg/m2, MGT intake and the presence of endometrial hyperplastic processes in the anamnesis.&#x0D; Conclusions. With prolonged use of sex steroids, there is a tendency to increase the risk of developing cancer of the female reproductive system. Careful follow-up and limitation of the duration of taking sex steroids in risk groups will reduce carcinogenic risks.

Identification of a novel cuproptosis-associated lncRNA model that can improve prognosis prediction in uterine corpus endometrial carcinoma

Uterine corpus endometrial carcinoma (UCEC) is a common female reproductive system cancer. Cuproptosis, a new type of mitochondrial respiration-regulated cell death, is associated with several cancer types. Here, we developed a cuproptosis-associated long non-coding RNA (lncRNA) model to predict the prognosis of patients with UCEC and their response to immune-based treatments. RNA sequencing (RNA-seq) and somatic mutation data for UCEC were obtained from The Cancer Genome Atlas (TCGA) database. LncRNAs co-expressed with cuproptosis-related genes were screened. Patients were randomly divided into two groups, one of which was used as training group to build the model, while the other group served as the validation group. A prognostic model comprising 13 cuproptosis-associated lncRNAs was constructed, and each lncRNA was individually related to patient prognosis. Our model clearly distinguished between risk variables in afflicted individuals. The risk score can provide a more accurate prognostic prediction compared with other clinical covariates. Patient groups at various risk groups were different according to tumor mutational burden and tumor immune dysfunction and exclusion analysis. We identified drugs for which patient populations at various risk groups showed higher sensitivity. Our model may contribute to immune related research and clinical decision-making for optimized treatment.

Metastasis Detection and Clinical Significance According to Localization of Resecting Lymph Nodes in Female Reproductive System Cancers

Metastasis Detection and Clinical Significance According to Localization of Resecting Lymph Nodes in Female Reproductive System Cancers

Evaluation of the Quality and Reliability of YouTube Videos With Turkish Content as an Information Source for Gynecological Cancers During the COVID-19 Pandemic.

Aim During the COVID-19 pandemic, YouTube became a critical information source for people seeking information about several diseases, including benign and malignant gynecological disorders. This study aimed to evaluate the quality and reliability of YouTube videos with Turkish content as an information source for gynecological cancers during the COVID-19 pandemic. Methods The research was performed between December 2nd and 5th, 2020. Two gynecologists searched the terms in Turkish; 'yumurtalık kanseri, COVID-19', 'rahim kanseri, coronavirus', 'rahim ağzı kanseri, COVID-19', 'kadın üreme sistemi kanseri, coronavirus', and 'jinekolojik kanserler, COVID-19'. on YouTube. 'Yumurtalık kanseri', 'rahim kanseri', 'rahim agzı kanseri', 'kadın üreme sistemi kanserleri' and 'jinekolojik kanserler' are the translations for "ovarian cancer, COVID-19", "endometrial cancer, coronavirus", "cervical cancer, COVID-19", "female reproductive system cancers, coronavirus", and "gynecological cancers, COVID-19" in the Turkish language, respectively. Videos were categorized into three groups depending on the upload source: the informative group, the personal experience group, and the news agency group. Moreover, DISCERN, the Medical Information and Content Index (MICI), the Video InformationandQuality Index (VIQI) were evaluated. Results A total of 57 videos were categorized as informative. Additionally, 22 videos and 18 videos were classified as patient experience videos and new agency videos, respectively. Patients who experienced videos had a significantly higher view number (p=0.001). The number of dislikes and DISCERN score were markedly better in favor of informative videos (p=0.009 and p=0.001). The MICI score was calculated as 13.0±1.8 for informative videos. The total VIQI score was 11.9 for informative videos, 8.8 for patient experience videos, and 7.2 for new agency videos (p = 0.001). Conclusions YouTube videos with Turkish content about gynecological cancers are easily accessible resources during the COVID-19 pandemic. Patient-published videos are the most preferred YouTube videos by Turkish citizens, and informative videos have a considerably lower dislike rate. According to the MICI score and significantly better DISCERN and VIQI scores, informative videos have acceptable quality.

Glutamine and amino acid metabolism as a prognostic signature and therapeutic target in endometrial cancer.

Endometrial cancer (EC) is the most common female reproductive system cancer in developed countries with growing incidence and associated mortality, which may be due to the growing prevalence of obesity. Metabolism reprogramming including glucose, amino acid, and lipid remodeling is a hallmark of tumors. Glutamine metabolism has been reported to participate in tumor proliferation and development. This study aimed to develop a glutamine metabolism-related prognostic model for EC and explore potential targets for cancer treatment. Transcriptomic data and survival outcome of EC were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes related to glutamine metabolism were recognized and utilized to build a prognostic model by univariate and multivariate Cox regressions. The model was confirmed in the training, testing, and the entire cohort. A nomogram combing prognostic model and clinicopathologic features was established and tested. Moreover, we explored the effect of a key metabolic enzyme, PHGDH, on the biological behavior of EC cell lines and xenograft model. Five glutamine metabolism-related genes, including PHGDH, OTC, ASRGL1, ASNS, and NR1H4, were involved in prognostic model construction. Kaplan-Meier curve suggested that patients recognized as high risk underwent inferior outcomes. The receiver operating characteristic (ROC) curve showed the model was sufficient to predict survival. Enrichment analysis recognized DNA replication and repair dysfunction in high-risk patients whereas immune relevance analysis revealed low immune scores in the high-risk group. Finally, a nomogram integrating the prognostic model and clinical factors was created and verified. Further, knockdown of PHGDH showed cell growth inhibition, increasing apoptosis, and reduced migration. Promisingly, NCT-503, a PHGDH inhibitor, significantly repressed tumor growth in vivo (p = 0.0002). Our work established and validated a glutamine metabolism-related prognostic model that favorably evaluates the prognosis of EC patients. DNA replication and repair may be the crucial point that linked glutamine metabolism, amino acid metabolism, and EC progression. High-risk patients stratified by the model may not be sufficient for immune therapy. PHGDH might be a crucial target that links serine metabolism, glutamine metabolism as well as EC progression.

Effects of miR-9-5p on the migration, invasion and epithelial-mesenchymal transition process in cervical squamous cell carcinoma.

Cervical squamous cell carcinoma is the most common cancer in female reproductive system. This study aims to explore the effect of microRNA-9-5p (miR-9-5p) on the migration, invasion, and epithelial-mesenchymal transition (EMT) process of cervical squamous cells. Bioinformatics were used to predict the miRNAs that could bind to E-cadherin (E-cad). The Cancer Genome Atlas (TCGA) database was used to analyze and extract significantly differentially expressed miRNAs from part of cervical squamous cell carcinoma tissues and normal cervical tissues, and miR-9-5p was selected as the main research target. The translated regions (UTR) of wild-type E-cad (E-cad-WT 3'-UTR) or the 3'-UTR of mutant E-cad (E-Cad-MUT 3'-UTR) was transfected with miR-9-5p mimic normal control (NC), and miR-9-5p mimic was co-transfected human embryonic kidney cells (293T). The relationship between miR-9-5p and E-cad was detected by double luciferase assay. The expression of miR-9-5p in normal cervical epithelial cell lines (H8) and cervical squamous cell lines (C33A, siha, caski and Me180) were detected by quantitative real-time PCR. Then, the experiments were divided into groups as follows: a block control group, an overexpression control group (mimic-NC group), a miR-95p overexpression group (mimic group), an inhibitory expression control group (inhibitor-NC group), and a miR-9-5p inhibitory expression group (inhibitor group). The changes of migration ability were detected by scratch assay. Transwell invasion assay was used to analyze the changes of invasion ability, and the mRNA and protein changes of E-cad and vimentin were detected by quantitative real-time PCR and Western blotting. MiR-9-5p had a targeting binding relationship with E-cad. Compared with the normal cervical tissue H8 cell line, the miR-9-5p was highly expressed in cervical cancer cell lines (C33A, siha, caski and Me180) (all P<0.05). The luciferase activity of E-cad-MUT was increased compared with that of E-cad-WT in miR-9-5p mimic cells (P<0.05). Compared with the blank control group, the protein and mRNA expressions of E-cad were decreased in the miR-9-5p mimic group (both P<0.05), which were increased in the miR-9-5p inhibitor group (both P<0.05). Compared with H8 cell line, the miR-9-5p was highly expressed in the cervical squamous cell lines (all P<0.05). Compared with the mimic-NC group, the distance of wound healing, the number of caski and Me180 cells invaded below the membrane, and the mRNA and protein expressions of vimentin were all increased in the miR-9-5p mimic group (all P<0.05), while the mRNA and protein of E-cad were decreased (both P<0.05). Compared with the inhibitor-NC group, the distance of wound healing, the number of caski and Me180 cells invading the membrane, and the mRNA and protein expressions of vimentin were decreased in the miR-9-5p inhibitor group (all P<0.05), but the mRNA and protein expressions of E-cad were increased (both P<0.05). The miR-9-5p is highly expressed in cervical squamous cell carcinoma, which can increase the migration and invasion ability, and promote the EMT process of cancer cells.

E2F8 knockdown suppresses cell proliferation and induces cell cycle arrest via Wnt/β-Catenin pathway in ovarian cancer.

Ovarian cancer is one of the leading causes of death in female reproductive system cancers. However, the pathogenesis of ovarian cancer remains elusive. Our aim is to investigate the potential targets for ovarian cancer. Two microarray datasets were obtained from the Gene Expression Omnibus public database. Using R package limma, the differentially expressed genes (DEGs) were identified from the datasets. There were 95 overlapping DEGs in two microarray datasets. GO, KEGG pathway analysis, and protein-protein interaction (PPI) network analysis were carried out based on the DEGs. Wnt signaling pathway and cell cycle were enriched in the KEGG pathway analysis. Moreover, the top 10 hub genes with the most nodes were determined by PPI network analysis. E2F8, one of hub genes was positively linked to a bad outcome in ovarian cancer patients. Furthermore, E2F8 knockdown suppressed cell proliferation and induced cell cycle arrest in ovarian cancer. In addition, we found that silencing E2F8 inhibited the Wnt/β-catenin signaling pathway. In ovarian cancer cells with E2F8 knockdown, overexpressing β-catenin restored both the suppressed capacity of cell proliferation and cell cycle progression. Therefore, our results revealed that E2F8 had an involvement in the development of ovarian cancer which might act as a therapeutic target.

Potential serum metabolites and long‐chain noncoding RNA biomarkers for endometrial cancer tissue

Endometrial carcinoma (EC) is one of the most common tumors in the female reproductive system. There are nearly 200 000 new cases every year. It is the third most common gynecological malignant tumor leading to female death. The incidence rate is closely related to lifestyle, and the incidence rate varies in different regions. The incidence rate of EC is ranking the first in the female reproductive system cancer just second only to breast, lung, and colorectal cancer in North America and Europe and the incidence rate of EC is only second, followed by breast cancer and cervical cancer in China. The potential metabolic markers of endometrial cancer were screened by liquid chromatograph mass spectrometer (LC-MS), and the tissues of patients with hysteromyoma and endometrial cancer were sequenced to explore the relationship between the disease and change in the content of long-chain noncoding RNA (lncRNA). Serum and tissue samples were collected from patients with endometrial dysplasia, endometrial cancer stage I, and endometrial cancer stage III. The metabolites in all serum samples were extracted, and the metabolites in all samples were detected by LC-MS/MS technology. The Pareto-scaling method was used for normalization, and the MetaboAnalyst 4.0 software was used for different analyses. The T test between groups showed that p ≤ 0.05 was regarded as the metabolite with a difference. Further, the function of differential metabolites was determined by metabolite function enrichment and co-expression analysis. Meanwhile, the differentially expressed lncRNA was detected by Illumina second-generation high-throughput sequencing technology, and the expression was analyzed by DEGseq software. Different lncRNA were screened according to p < 0.05. LncRNA with significant differences were screened by p < 0.01, q < 0.001, fold change ≥2, and false discovery rate (FDR) ≤0.001. Through synthesis of T test, cluster heatmap, and ROC curve analysis, five biomarkers with potential diagnostic ability were obtained, including 2,3-Pyridinedicarboxylic acid (area under the curve (AUC)=0.69), Hematommic acid, ethyl ester (AUC=0.69), Maltitol (AUC=0.69), 13(S)-HODE (AUC=0.88), and D-Mannitol (AUC=0.69) had potential diagnostic ability between EC phase I versus EC phase III. At the same time, lncRNA sequencing results showed that when endometrial atypical hyperplasia continued to change, including LINC00511, PVT1, and IQCH-AS1 (downregulated), and only changed significantly in the endometrial dysplasia group, including MALAT1, CARMN (downregulated) and LINC00648, BISPR, LINC01534, and LINC00930 (upregulated). Moreover, both differential metabolites and differential lncRNA were annotated to the lipid metabolism pathway, suggesting that this pathway played an important role in the occurrence and development of endometrial carcinoma. It can combine the results of metabolomics and lncRNA sequencing to assist in the early diagnosis of endometrial precancerous lesions and endometrial cancer patients, to enhance the sensitivity and specificity of diagnosis, which has a certain clinical application prospect.

Prognostic Role of Hormone Status in Endometrium Cancer

Aim: Endometrial carcinoma (EC) is the most common female reproductive system cancer in Europe and fifth leading reason of death in female cancer in worldwide. Hormone receptors are the main modulator of endometrium functions. Aim of present study was to evaluate prognostic indicator Estrogen receptors (ER) and progesterone receptor (PR) in patients at FIGO stage 3 EC. &#x0D; &#x0D; Material and Methods: This study was designed as retrospective one institution analysis. ER status and PR status was enrolled from medical records of patients. Primary endpoint of this study was effect of hormone status to the disease-free survival (DFS) and overall survival (OS). &#x0D; &#x0D; Results: Present study enrolled 133 patients from January 2015 to October 2021. ER and hormone positivity were statistically significant in OS analysis (HR: 1.40 p:0.005 and HR:2.173 p: 0.047). PR status was insignificant statistically in both DFS and OS survival analysis (HR: 1.80 p:0.09 and HR: 1.72, p: 0.062 respectively). The median DFS and OS were 58 months (51-64) and 129 months (88-169) patients with ER positive tumor respectively (p

Impact of endocrine disrupting chemicals (EDCs) on the predisposition of cancer and polycystic ovary syndrome (PCOS): A Note

Endocrine Disrupting Chemicals (EDCs) or Endocrine Disruptors are unique assemblage or cluster of emerging pollutants as they affect the synthesis, release and transport of hormones. EDCs have been associated with a diverse array of health issues and diseases. EDCs can alter the endocrine system and are involved in carcinogenesis and inducing poly-cystic ovary syndrome (PCOS). The objective of this article is to furnish an outline of research on environmental aspects of EDCs and their effects on human health specially on cancer and PCOS based on evidence from animal and human studies. EDCs include natural compounds such as phytoestrogens and various synthetic chemicals which are utilized by the chemical, agriculture, cosmetic and food industries. Several EDCs may work as carcinogens and causes initiation and advancement of cancer. Uterine and ovarian cancers of female have been associated with exposure to EDC. Bisphenol-A (BPA), an EDC which is found in plastic bottles, household materials, canned food, waste water, beverage containers and thermal paper, can increase risk of breast cancer. Even low levels of BPA exposure may poses threat of prostate cancer in men. Testicular cancer and thyroid cancer could be influenced by EDCs. Comprehensive studies have been conducted by many researchers in the light of toxicity pattern of EDC that render interpretation of impact of EDCs on development of cancer and PCOS inducing capacity in female reproductive system.&#x0D; Keywords: Endocrine disrupting chemicals; EDC; Cancer; Endocrine Disruptor, Poly-Cystic Ovary Syndrome; PCOS

Synergism between the metabolic syndrome components and cancer incidence: results from a prospective nested case–control study based on the China Health and Retirement Longitudinal Study (CHARLS)

ObjectivesSynergism between the metabolic syndrome (MetSyn) components and cancer incidence still remains inconclusive. We aimed to investigate the unique or joint role of MetSyn components in cancer onset.DesignWe conducted a...

Increased expression of MMP17 predicts poor clinical outcomes in epithelial ovarian cancer patients.

Ovarian cancer has the highest fatality rate among female reproductive system cancers, which is due to lack of biomarker for diagnosis and prognosis. We aimed to evaluate the role of matrix metalloproteinase 17 (MMP17) in ovarian cancer tumorigenesis and prognosis. Based on the epithelial ovarian cancer (EOC) in The Cancer Genome Atlas database, we determined the expression of MMP17 using the Wilcoxon rank-sum test. The biological functions of MMP17 were evaluated using the Metascape database and Gene Set Enrichment Analysis. The association between MMP17 and immune cell infiltration was investigated by single sample Gene Set Enrichment Analysis. Logistic analysis was applied to study the correlation between MMP17 expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan–Meier analysis, and nomograms were used to determine the predictive value of MMP17 on clinical outcomes in EOC patients. The expression of MMP17 was much higher in EOC patients than in pericarcinomatous tissues (P < .001). MMP17-associated differentially expressed genes were significantly enriched in cell extracellular matrix (ECM) degrading and corresponding pathways in the high MMP17 expression phenotype. MMP17 has a high sensitivity and specificity for EOC diagnosis, with an area under the curve of 0.988. MMP17 expression was found to be an independent risk factor for overall survival (hazard ratio [HR]: 1.488, P < .001), progression-free interval (HR: 1.347, P < .01), and disease-specific survival (HR: 1.548, P < .01). Increased MMP17 expression in EOC may contribute to carcinogenesis by degrading ECM and provide diagnostic and prognostic value for clinical outcomes.

Molecular Regulation of Androgen Receptors in Major Female Reproductive System Cancers.

There are three main types of cancer in the female reproductive system, specifically ovarian cancer (OVCA), endometrial cancer (EC), and cervical cancer (CC). They are common malignant tumors in women worldwide, with high morbidity and mortality. In recent years, androgen receptors (ARs) have been found to be closely related to the occurrence, progression, prognosis, and drug resistance of these three types of tumors. This paper summarizes current views on the role of AR in female reproductive system cancer, the associations between female reproductive system cancers and AR expression and polymorphisms. AR regulates the downstream target genes transcriptional activity and the expression via interacting with coactivators/corepressors and upstream/downstream regulators and through the gene transcription mechanism of “classical A/AR signaling” or “non-classical AR signaling”, involving a large number of regulatory factors and signaling pathways. ARs take part in the processes of cancer cell proliferation, migration/invasion, cancer cell stemness, and chemotherapeutic drug resistance. These findings suggest that the AR and related regulators could target the treatment of female reproductive system cancer.

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer.

With a rich abundance of natural polyphenols, green tea has become one of the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the predominant catechin found in green tea, which has been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, and anticancer. Clinical studies have also shown the inhibitory effects of EGCG on cancers of the male and female reproductive system, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Autophagy is a natural, self-degradation process that serves important functions in both tumor suppression and tumor cell survival. Naturally derived products have the potential to be an effective and safe alternative in balancing autophagy and maintaining homeostasis during tumor development. Although EGCG has been shown to play a critical role in the suppression of multiple cancers, its role as autophagy modulator in cancers of the male and female reproductive system remains to be fully discussed. Herein, we aim to provide an overview of the current knowledge of EGCG in targeting autophagy and its related signaling mechanism in reproductive cancers. Effects of EGCG on regulating autophagy toward reproductive cancers as a single therapy or cotreatment with other chemotherapies will be reviewed and compared. Additionally, the underlying mechanisms and crosstalk of EGCG between autophagy and other cellular processes, such as reactive oxidative stress, ER stress, angiogenesis, and apoptosis, will be summarized. The present review will help to shed light on the significance of green tea as a potential therapeutic treatment for reproductive cancers through regulating autophagy.

IGF2BP3‑stabilized SIX4 promotes the proliferation, migration, invasion and tube formation of ovarian cancer cells.

The mortality rate of ovarian cancer (OC) is the highest among the different types of female reproductive system cancers. SIX homeobox 4 (SIX4), a member of the homeobox family, subfamily SIX, fulfills an important role in metastasis and angiogenesis in a variety of types of cancer. The aim of the present study was to investigate both the effects and the underlying mechanism of SIX4 on angiogenesis in OC. The Gene Expression Profiling Interactive Analysis and Encyclopedia of RNA Interactomes databases were employed to predict the expression levels of SIX4 in OC tissues, and its association with the overall survival (OS) rate of patients with OC. The expression levels of SIX4 in OC cell lines were detected by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Following silencing of SIX4, the proliferation, invasion, migration and angiogenesis of OC cells were investigated via Cell Counting Kit-8, colony formation, wound healing, Transwell and tube formation assays. Subsequently, the levels of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in OC cell lines were detected by RT-qPCR and western blot analysis. The ability of IGF2BP3 to bind to SIX4 mRNA was detected via an RNA immunoprecipitation assay, and the stability of SIX4 mRNA was assessed by RT-qPCR following Actinomycin D treatment. Finally, the effects of transfection of sh-SIX4 and overexpression of IGF2BP3 simultaneously were examined to further delineate the mechanism involved. It was revealed that SIX4 was highly expressed in OC tissues and cells, and its expression was associated with low OS rates in patients with OC. SIX4 knockdown with short hairpin RNA inhibited the proliferation, migration and invasion of cells, as well as angiogenesis. In addition, IGF2BP3 overexpression led to an improvement in the stability of SIX4 mRNA. Overexpression of IGF2BP3 also reversed the inhibitory effect of SIX4 interference on the malignant phenotypes of OC cells. Taken together, the results of the present study demonstrated that IGF2BP3-stabilized SIX4 promoted the proliferation, metastasis and angiogenesis of SKOV3 cells.

The prognostic and clinicopathological significance of desmoglein 2 in human cancers: a systematic review and meta-analysis.

ObjectiveThe survival and clinicopathological significance of desmoglein 2 (DSG2) in various cancers is controversial. Thus, we performed this systematic review and meta-analysis to explore the preliminary prognostic value of DSG2.MethodsEligible studies were identified from databases including PubMed, the Cochrane Library, Embase, Web of Science and Scopus. Hand searches were also conducted in relevant bibliographies. We then extracted and pooled hazard ratio (HR) of overall survival (OS) and odds ratio (OR) of clinicopathological features.ResultsA total of 11 eligible studies containing 1,488 patients were included. Our results demonstrated that in non-small cell lung cancer (NSCLC), high DSG2 expression is associated with poor OS. However, in digestive system cancer and female reproductive system cancer, there were no statistically significant associations between OS and DSG2.ConclusionsBased on the findings of this study, high DSG2 expression is associated with worse prognosis in patients with NSCLC, and thus DSG2 expression could be a biomarker for prognosis in NSCLC.

Work with cancer or stop working after diagnosis? Variables affecting the decision.

Studies about work and cancer predominantly considered the return to work of cancer survivors. However, some studies highlighted that many patients work with cancer even immediately after the diagnosis. Little is known about the frequency, causes, and consequences of this behavior. This study aimed to estimate how many cancer patients continue working in the month after the diagnosis in an Italian context and to determine which factors affect the decision to stop working in the same period. One hundred seventy-six patients with breast, gastrointestinal, prostate, or female reproductive system cancer completed a survey with demographic, occupational, and psychosocial information. Clinical information was collected from medical records. We measured how many workers continued working in the month after cancer diagnosis without substantial interruptions and selected the best logistic regression model of this behavior's predictors. Sixty-eight percent of the patients continued working in the month after the diagnosis. Patients were more likely to stop working with a higher level of perceived work-health incompatibility (OR = 2.64; 95%CI: 1.48-4.69), an open-ended contract (OR = 3.20; CI: 1.13-9.09), and a complex treatment (surgery+chemo-/radio-therapy, OR = 4.25; CI: 1.55-11.65) and less likely with breast cancer (OR = 0.20; CI: 0.07-0.56), and more children (OR = 0.59; CI: 0.37-0.96). To continue working with cancer is a common practice among the newly diagnosed. The decision to suspend work activity relates to evaluating how much work activities hamper one's health care needs and the practical difficulties expected in handling cancer care and work.