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A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours

Russell, MR; Graham, C; D'Amato, A; Gentry-Maharaj, A; Ryan, A; Kalsi, JK; Ainley, C; ... Graham, RLJ; + view all (2017) A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours. British Journal of Cancer , 117 (5) pp. 666-674. 10.1038/bjc.2017.199. Green open access

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Abstract

BACKGROUND: There is an urgent need for biomarkers for the early detection of ovarian cancer (OC). The purpose of this study was to assess whether changes in serum levels of lecithin-cholesterol acyltransferase (LCAT), sex hormone-binding globulin (SHBG), glucose-regulated protein, 78 kDa (GRP78), calprotectin and insulin-like growth factor-binding protein 2 (IGFBP2) are observed before clinical presentation and to assess the performance of these markers alone and in combination with CA125 for early detection. METHODS: This nested case-control study used samples from the United Kingdom Collaborative Trial of Ovarian Cancer Screening trial. The sample set consisted of 482 serum samples from 49 OC subjects and 31 controls, with serial samples spanning up to 7 years pre-diagnosis. The set was divided into the following: (I) a discovery set, which included all women with only two samples from each woman, the first at<14 months and the second at >32 months to diagnosis; and (ii) a corroboration set, which included all the serial samples from the same women spanning the 7-year period. Lecithin-cholesterol acyltransferase, SHBG, GRP78, calprotectin and IGFBP2 were measured using ELISA. The performance of the markers to detect cancers pre-diagnosis was assessed. RESULTS: A combined threshold model IGFBP2 >78.5 ng ml(-1) : LCAT <8.831 μg ml(-1) : CA125 >35 U ml(-1) outperformed CA125 alone for the earlier detection of OC. The threshold model was able to identify the most aggressive Type II cancers. In addition, it increased the lead time by 5-6 months and identified 26% of Type I subjects and 13% of Type II subjects that were not identified by CA125 alone. CONCLUSIONS: Combined biomarker panels (IGFBP2, LCAT and CA125) outperformed CA125 up to 3 years pre-diagnosis, identifying cancers missed by CA125, providing increased diagnostic lead times for Type I and Type II OC. The model identified more aggressive Type II cancers, with women crossing the threshold dying earlier, indicating that these markers can improve on the sensitivity of CA125 alone for the early detection of OC.

Type: Article
Title: A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive type II tumours
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/bjc.2017.199
Publisher version: http://doi.org/10.1038/bjc.2017.199
Language: English
Additional information: Copyright © The Author(s) named above 2017This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Ovarian cancer; early detection; biomarkers
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery.ucl.ac.uk/id/eprint/1565179
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