Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer

Elsharawy, Khloud A.; Althobiti, Maryam; Mohammed, Omar J.; Aljohani, Abrar I.; Toss, Michael S.; Green, Andrew R.; Rakha, Emad

Abstract

Purpose
Nucleolar protein 10 (NOP10) is required for ribosome biogenesis and telomere maintenance and plays a key role in carcinogenesis. This study aims to evaluate the clinical and prognostic significance of NOP10 in breast cancer (BC).

Methods
NOP10 expression was assessed at mRNA level employing the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1980) and Cancer Genome Atlas (TCGA) BC cohorts (n = 854). Protein expression was evaluated on tissue microarray of a large BC cohort (n = 1081) using immunohistochemistry. The correlation between NOP10 expression, clinicopathological parameters and patient outcome was assessed.

Results
NOP10 expression was detected in the nucleus and nucleolus of the tumour cells. At the transcriptomic and proteomic levels, NOP10 was significantly associated with aggressive BC features including high tumour grade, high nucleolar score and poor Nottingham Prognostic Index. High NOP10 protein expression was an independent predictor of poor outcome in the whole cohort and in triple-negative BC (TNBC) class (p = 0.002 & p = 0.014, respectively). In chemotherapy- treated patients, high NOP10 protein expression was significantly associated with shorter survival (p = 0.03) and was predictive of higher risk of death (p = 0.028) and development of distant metastasis (p = 0.02) independent of tumour size, nodal stage and tumour grade.

Conclusion
High NOP10 expression is a poor prognostic biomarker in BC and its expression can help in predicting chemotherapy resistance. Functional assessments are necessary to decipher the underlying mechanisms and to reveal its potential therapeutic values in various BC subtypes especially in the aggressive TNBC class.

Citation

Elsharawy, K. A., Althobiti, M., Mohammed, O. J., Aljohani, A. I., Toss, M. S., Green, A. R., & Rakha, E. (2021). Nucleolar protein 10 (NOP10) predicts poor prognosis in invasive breast cancer. Breast Cancer Research and Treatment, 185(3), 615-627. https://doi.org/10.1007/s10549-020-05999-3

• Journal Article Type: Article
• Acceptance Date: Oct 26, 2020
• Online Publication Date: Nov 8, 2020
• Publication Date: 2021-02
• Deposit Date: Oct 27, 2020
• Publicly Available Date: Nov 9, 2021
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 185
• Issue: 3
• Pages: 615-627
• DOI: https://doi.org/10.1007/s10549-020-05999-3
• Keywords: NOP10; invasive breast cancer; nucleoli; prognosis
• Public URL: https://nottingham-repository.worktribe.com/output/4993715
• Publisher URL: https://link.springer.com/article/10.1007/s10549-020-05999-3
• Additional Information: Received: 14 August 2020; Accepted: 26 October 2020; First Online: 8 November 2020; : ; : All the authors declare that they have no conflict of interest.; : This study was approved by the Nottingham Research Ethics Committee 2 under the title ‘Development of a molecular genetic classification of breast cancer’ and the North West – Greater Manchester Central Research Ethics Committee under the title ‘Nottingham Health Science Biobank (NHSB)’ reference number 15/NW/0685. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Release of data was also pseudoanonymised as per the UK Human Tissue Act regulations. This article does not contain any studies with animals performed by any of the authors.; : Informed consent was obtained from all individuals prior to surgery to use their tissue materials in research.