Oncotarget

Research Papers:

High mobility group protein B1 is a predictor of poor survival in ovarian cancer

Lee R. Machado _, Paul M. Moseley, Robert Moss, Suha Deen, Christopher Nolan, Ian Spendlove, Judith M. Ramage, Stephen YT. Chan and Lindy G. Durrant

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Oncotarget. 2017; 8:101215-101223. https://doi.org/10.18632/oncotarget.20538

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Abstract

Lee R. Machado1,5,6,**, Paul M. Moseley4,**, Robert Moss2, Suha Deen3, Christopher Nolan2, Ian Spendlove2, Judith M. Ramage2,*, Stephen YT. Chan4,* and Lindy G. Durrant2,*

1Faculty of Health and Society, University of Northampton, Boughton Green Road, Northampton, NN2 7AL, United Kingdom

2Academic Department of Clinical Oncology, Division of Cancer and Stem cells, City Hospital Campus, University of Nottingham, Nottingham NG5 1PB, UK

3Department of Histopathology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre Campus Division of Clinical Pathology Division of Clinical Oncology, School of Molecular Medical Sciences, University of Nottingham, City Hospital Campus, Nottingham NG5 1PB, UK

4Clinical Oncology Department, Nottingham University Hospitals, Nottingham NG5 1PB, UK

5Department of Genetics, University of Leicester, Leicester, LE1 7RH, UK

6Faculty of Science, Technology, Engineering & Mathematics, The Open University, Milton Keynes, MK7 6AA, UK

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Correspondence to:

Lee R. Machado, email: [email protected]

Keywords: HMGB1; autophagy; ovarian cancer; prognostic; DAMP

Received: January 06, 2017    Accepted: August 07, 2017    Published: August 24, 2017

ABSTRACT

High-mobility group protein B1 (HMGB1) has been implicated in numerous tumour types where expression regulates tumour cell growth and survival. We hypothesised that high HMGB1 expression in ovarian tumours would predict poor patient survival.

Using tissue microarrays of primary ovarian cancers combined with a comprehensive database of clinicopathological variables, the expression of HMGB1 was assessed by immunohistochemistry in two independent cohorts (n=194 and n=360) using a monoclonal antibody specific for HMGB1.

Kaplan-Meier analysis showed an association of HMGB1 expression with progression free survival in the primary cohort (p=0.023). In the validation cohort, expression was associated with overall survival (p=0.002). Low expression of HMGB1 was protective and in a multivariate model HMGB1 expression was shown to be an independent predictor of poor survival in ovarian cancer (p=0.006).

The role of HMGB1 in cancer is complex. As high levels of HMGB1 expression are likely to render ovarian cancer cells resistant to chemotherapy, therapies targeting the HMGB1 axis may be appropriate in the treatment of ovarian cancer patients.


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