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PMID: 33473167 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Discovery of a biomarker candidate for surgical stratification in high-grade serous ovarian cancer.

British journal of cancer ·Vol. 124 ·No. 7 ·2021-00-00 ·Pages 1286-1293

Lu H, Cunnea P, Nixon K, Rinne N, Aboagye EO, Fotopoulou C

Abstract

Maximal effort cytoreductive surgery is associated with improved outcomes in advanced high-grade serous ovarian cancer (HGSOC). However, despite complete gross resection (CGR), there is a percentage of patients who will relapse and die early. The aim of this study is to identify potential candidate biomarkers to help personalise surgical radicality. 136 advanced HGSOC cases who underwent CGR were identified from three public transcriptomic datasets. Candidate prognostic biomarkers were discovered in this cohort by Cox regression analysis, and further validated by targeted RNA-sequencing in HGSOC cases from Imperial College Healthcare NHS Trust (n = 59), and a public dataset. Gene set enrichment analysis was performed to understand the biological significance of the candidate biomarker. We identified ALG5 as a prognostic biomarker for early tumour progression in advanced HGSOC despite CGR (HR = 2.42, 95% CI (1.57-3.75), p < 0.0001). The prognostic value of this new candidate biomarker was additionally confirmed in two independent datasets (HR = 1.60, 95% CI (1.03-2.49), p = 0.0368; HR = 3.08, 95% CI (1.07-8.81), p = 0.0365). Mechanistically, the oxidative phosphorylation was demonstrated as a potential biological pathway of ALG5-high expression in patients with early relapse (p < 0.001). ALG5 has been identified as an independent prognostic biomarker for poor prognosis in advanced HGSOC patients despite CGR. This sets a promising platform for biomarker combinations and further validations towards future personalised surgical care.

MeSH Terms
Biomarkers, Tumor/genetics,metabolism Cystadenocarcinoma, Serous/metabolism,pathology,surgery Cytoreduction Surgical Procedures/mortality Female Follow-Up Studies Humans Middle Aged Ovarian Neoplasms/metabolism,pathology,surgery Prognosis Retrospective Studies Survival Rate
Chemicals
Biomarkers, Tumor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lu Haonan
Department of Surgery and Cancer, Division of Cancer, Faculty of Medicine, Imperial College London, London, W12 0HS, UK. | Department of Surgery and Cancer, Cancer Imaging Centre, Faculty of Medicine, Imperial College London, London, W12 0HS, UK.
Cunnea Paula
Department of Surgery and Cancer, Division of Cancer, Faculty of Medicine, Imperial College London, London, W12 0HS, UK.
Nixon Katherine
Department of Surgery and Cancer, Division of Cancer, Faculty of Medicine, Imperial College London, London, W12 0HS, UK.
Rinne Natasha
Department of Surgery and Cancer, Division of Cancer, Faculty of Medicine, Imperial College London, London, W12 0HS, UK.
Aboagye Eric O
Department of Surgery and Cancer, Division of Cancer, Faculty of Medicine, Imperial College London, London, W12 0HS, UK. | Department of Surgery and Cancer, Cancer Imaging Centre, Faculty of Medicine, Imperial College London, London, W12 0HS, UK.
Fotopoulou Christina ORCID
Department of Surgery and Cancer, Division of Cancer, Faculty of Medicine, Imperial College London, London, W12 0HS, UK. c.fotopoulou@imperial.ac.uk.
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
1532-1827
DOI
10.1038/s41416-020-01252-2
Email
c.fotopoulou@imperial.ac.uk
Published
2021-00-00
Epub
2021-00-21
Pages
1286-1293
Language
English
Region
England
NLM ID
0370635
PMCID
PMC8007618
Subset
IM
Grants
Medical Research Council · MR/J007986/1 · United Kingdom
External Links
PubMed source DOI: 10.1038/s41416-020-01252-2 PMC Full Text View journal details
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