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

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

doi:10.1007/s10549-020-05999-3

Abstract

PurposeNucleolar 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).MethodsNOP10 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.ResultsNOP10 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.ConclusionHigh 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.

Highlights

Invasive breast cancer (BC) is a heterogeneous disease with a spectrum of different molecular and morphological subtypes that are variable in behaviour and response to therapy [1]
When the members in H/ACA RNPs box were analysed at the transcriptomic levels in both the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (n = 1980) and The Cancer Genome Atlas (TCGA) BC dataset (n = 854), Nucleolar protein 10 (NOP10) was highly associated with aggressive tumour features and worse patient outcome, compared to others
High NOP10 mRNA expression was significantly associated with features characteristic of poor prognosis including younger age, higher tumour grade, poorer Nottingham prognostic index (NPI) scores, hormone receptor negativity, human epidermal growth factor 2 (HER2) positivity, triple-negative BC (TNBC) phenotype and advance nodal stage (p = 0.001)

Summary

Introduction

Invasive breast cancer (BC) is a heterogeneous disease with a spectrum of different molecular and morphological subtypes that are variable in behaviour and response to therapy [1]. Morphological features such as histological grade have a prognostic value and their assessment help in treatment decisions of BC patients [2]. Alterations in the nucleolus during tumourigenesis usually take place as a consequence of elevating ribosomal biogenesis to subtend the high demand for proteins in cancer cells which is highly required for their proliferation [5, 6]. Dysregulation of snoRNPs can influence the development and progression of various human diseases such as Prader Willi syndrome, some metabolic stress disorders, and several types of cancer [8,9,10,11]

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