Endometrial cancer (EC) is the most common gynaecological malignancy. Nucleolin (NCL) is involved in rDNA transcription, cell proliferation, and apoptosis, with high expression associated with worse overall survival (OS) in other adenocarcinomas. Our aims were to assess NCL gene and protein expression and explore the differential expression of NCL-associated genes (NAGs) in endometrial carcinogenesis. Endometrial samples were obtained from 157 women to include healthy, hyperplastic (EH), EC, and metastatic groups. RT-qPCR and immunohistochemistry were employed to assess NCL gene and protein levels. In silico analysis of NAGs in TCGA and GEO datasets was performed, with the prognostic value determined via Human Protein Atlas. NCL mRNA level of EC was lower than in healthy post-menopausal endometrium (p < 0.01). EH samples had lower NCL immuno-expression scores than healthy pre-menopausal (p < 0.001), benign post-menopausal (p < 0.01), and EC (p < 0.0001) samples. Metastatic lesions demonstrated higher NCL quick scores than primary tissue (p = 0.04). Higher NCL Immuno quick scores carried a worse OS in high-grade EC (p = 0.01). Interrogating Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and Uterine Carcinosarcoma (TCGA-UCS) cohorts revealed NCL to be the most highly upregulated gene in carcinosarcoma, with S100A11, LMNB2, RERG, E2F1 and CCNA2 representing key dysregulated NAGs in EC. Since NCL is implicated in transforming hyperplastic glands into cancer, with further involvement in metastasis, it is suggested to be a promising target for better-informed diagnosis, risk stratification, and management of EC.
Background Polycystic Ovary Syndrome is a chronic and a common gynaecological condition impacting women of reproductive age. Women with PCOS have hormonal, ovulatory and metabolic dysfunction resulting in multiple symptoms. The correlation between hormonal disbalance and the impact on womens mental health has been researched for decades. However, the prevalence among different ethnicities has not been fully evaluated. Methods A systematic methodology was developed, and a protocol was published in PROSPERO CRD42020210863 and a systematic review of publications between 1st January 1990 30th January 2021 was conducted. Multiple electronic databases were explored using keywords and MeSH terms. The finalised dataset was analysed using statistical methods such as random effect models, subgroup analysis and sensitivity analysis. Findings We included 30 studies reporting on 3944 PCOS women. Majority of studies addressed depression anxiety, and common mental health. Studies had fair to poor methodological quality and includes observational studies and Randomised Clinical Trials. Overall, 17% 95% CI 7% to 29% of women with PCOS have clinical diagnosis of major or severe depression; 33% 95% CI 26% to 40% have elevated depressive symptoms or a clinical diagnosis of depression; 41% 95% CI 28% to 54% report anxiety symptoms, and 31% 95% CI 15% to 51% have a form a common mental health or are taking psychiatric medication for anxiety and / or depression. The use of various tools to assess mental health symptoms was among the reasons for the substantial heterogeneity across studies. Interpretation PCOS is associated with an increased risk of mental health disorders including depressives, anxiety, and other mental health disorders. While BAME populations account for about 20% of most of the samples studied, stratification by ethnicity was rarely attempted which made it difficult to elucidate the MH impact of PCOS on different communities.
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