Barzilova, Vanya D, Drury, Josephine 
ORCID: 0000-0002-2275-6664, Rogers, Bryony, Thomas, Emily, Ahmed, Fareen, Bradfield, Alice, Al-Lamee, Hannan and Hapangama, Dharani K ORCID: 0000-0003-0270-0150
(2022)
Role of Nucleolin in Endometrial Precancerous Hyperplasia and Carcinogenesis: Ex Vivo and In Silico Study.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23 (11).
6228-.
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Role of Nucleolin in Endometrial Precancerous Hyperplasia and Carcinogenesis Ex Vivo and In Silico Study.pdf - Published version Download (3MB) | Preview |
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | endometrial cancer, nucleolin, metastasis |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Clinical Directorate Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 08 Jul 2022 14:13 |
| Last Modified: | 16 Mar 2023 19:34 |
| DOI: | 10.3390/ijms23116228 |
| Open Access URL: | https://doi.org/10.3390/ijms23116228 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3158034 |
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