Evidence map›Paper›PMID 39182365›Full record

ArticleTranslational oncology2024

Low cytoplasmic NUB1 protein exerts hypoxic cell death with poorer prognosis in oestrogen receptor negative breast cancer patients.

Ka-Liong Tan, Syed Haider, Christos E Zois, Jianting Hu, Helen Turley, Russell Leek, Francesca Buffa, Oreste Acuto, Adrian L Harris, Francesco Pezzella

Erratum issuedAbstract read
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In one paragraph

Article in Translational oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Ka-Liong TanTumour Pathology Laboratory, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK; Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia (USIM), Persiaran Ilmu, Putra Nilai, 71800 Nilai, Negeri Sembilan, Malaysia. Electronic address: kaliong_tan@usim.edu.my.
Syed HaiderDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK; Computational Biology and Integrative Genomics, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive Oxford, University of Oxford, UK; The Breast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK. Electronic address: Syed.Haider@icr.ac.uk.
Christos E ZoisDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Jianting HuTumour Pathology Laboratory, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
Helen TurleyDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Russell LeekDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Francesca BuffaComputational Biology and Integrative Genomics, Department of Oncology, Old Road Campus Research Building, Roosevelt Drive Oxford, University of Oxford, UK.
Oreste AcutoLaboratory of T-cell signalling, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Adrian L HarrisDepartment of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
Francesco PezzellaTumour Pathology Laboratory, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. Electronic address: francesco.pezzella@ndcls.ox.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Current prognostic biomarkers fall short in stratifying Oestrogen receptor (ER)-negative breast cancer patients regarding tumour progression risk at diagnosis. The role of AIPL1 in activating its tumour suppressor client protein, NEDD8 Ultimate Buster-1 (NUB1) remains unknown in cancer. Our study demonstrated how downregulated AIPL1 results in the deactivated NUB1 protein under hypoxic conditions. We examined the AIPL1-NUB1 pathwayin vitro using cell lines i.e. MCF-7, MDA-MB-231, RCC4 etc. NUB1 expression was assessed using Oncomine, and cBioPortal was performed to assess NUB1's prognostic significance in human cancers. In the John Radcliffe Hospital cohort (n = 122), immunohistochemistry analysis revealed downregulated AIPL1 (Log2 fold change=-0.28; p < 0.001) and upregulated NUB1 transcripts (Log2 fold change=0.59; p < 0.001) compared to adjacent normal tissues. In severe chronic hypoxia, multimerised AIPL1 localisedin the cytoplasm while NUB1 protein migrated to the nucleus, where the absence of NUB1 nuclear localisation led to cell cycle arrest. Biopsies showed that patients with lower cytoplasmic NUB1 expression (n = 57) had poorer overall survival compared to those with higher cytoplasmic expression (n = 57), HR=1.78; 95 % CI=1.01-3.35, p = 0.048. Low NUB1 protein levels in both normoxic and hypoxic conditions were associated with cell cycle arrest and upregulation ofp21 and p27 in breast cancer cell lines, correlating significantly withpoorer survival outcomes in all breast cancer and ER-negative breast cancer patients.

Indexed as

BiomarkersImmunohistochemistryNUB1Oestrogen receptor

Identifiers

PMID39182365
PMCPMC11387679

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.