Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas

Statistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cel...

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Main Authors: Andreas Kleppe, Fritz Albregtsen, Jone Trovik, Gunnar B. Kristensen, Håvard E. Danielsen
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/12/3838
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author Andreas Kleppe
Fritz Albregtsen
Jone Trovik
Gunnar B. Kristensen
Håvard E. Danielsen
author_facet Andreas Kleppe
Fritz Albregtsen
Jone Trovik
Gunnar B. Kristensen
Håvard E. Danielsen
author_sort Andreas Kleppe
collection DOAJ
description Statistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cell nuclei. The aim was to investigate the prognostic value of such an assessment in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. The diversity was quantified by calculating the entropy of both chromatin compartment sizes and optical densities within compartments. We analysed a median of 281 nuclei (interquartile range (IQR), 273 to 289) from 246 ovarian carcinoma patients and a median of 997 nuclei (IQR, 502 to 1452) from 791 endometrial carcinoma patients. The prognostic value of the entropies and chromatin heterogeneity was moderately strongly correlated (<i>r</i> ranged from 0.68 to 0.73), but the novel marker was observed to provide additional prognostic information. In multivariable analysis with clinical and pathological markers, the hazard ratio associated with the novel marker was 2.1 (95% CI, 1.3 to 3.5) in ovarian carcinoma and 2.4 (95% CI, 1.5 to 3.9) in endometrial carcinoma. Integration with pathological risk classifications gave three risk groups with distinctly different prognoses. This suggests that the novel marker of diversity of chromatin compartments might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and low-risk endometrial carcinoma patients for less extensive surgery.
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spelling doaj.art-e908c1d73632484cb870334f29c95b0c2023-11-21T01:38:26ZengMDPI AGCancers2072-66942020-12-011212383810.3390/cancers12123838Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological CarcinomasAndreas Kleppe0Fritz Albregtsen1Jone Trovik2Gunnar B. Kristensen3Håvard E. Danielsen4Institute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424 Oslo, NorwayInstitute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424 Oslo, NorwayDepartment of Obstetrics and Gynecology, Haukeland University Hospital, NO-5020 Bergen, NorwayInstitute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424 Oslo, NorwayInstitute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424 Oslo, NorwayStatistical texture analysis of cancer cell nuclei stained for DNA has recently been used to develop a pan-cancer prognostic marker of chromatin heterogeneity. In this study, we instead analysed chromatin organisation by automatically quantifying the diversity of chromatin compartments in cancer cell nuclei. The aim was to investigate the prognostic value of such an assessment in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. The diversity was quantified by calculating the entropy of both chromatin compartment sizes and optical densities within compartments. We analysed a median of 281 nuclei (interquartile range (IQR), 273 to 289) from 246 ovarian carcinoma patients and a median of 997 nuclei (IQR, 502 to 1452) from 791 endometrial carcinoma patients. The prognostic value of the entropies and chromatin heterogeneity was moderately strongly correlated (<i>r</i> ranged from 0.68 to 0.73), but the novel marker was observed to provide additional prognostic information. In multivariable analysis with clinical and pathological markers, the hazard ratio associated with the novel marker was 2.1 (95% CI, 1.3 to 3.5) in ovarian carcinoma and 2.4 (95% CI, 1.5 to 3.9) in endometrial carcinoma. Integration with pathological risk classifications gave three risk groups with distinctly different prognoses. This suggests that the novel marker of diversity of chromatin compartments might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and low-risk endometrial carcinoma patients for less extensive surgery.https://www.mdpi.com/2072-6694/12/12/3838chromatin compartmentschromatin organisationtexture analysisprognostic markerovarian cancerendometrial cancer
spellingShingle Andreas Kleppe
Fritz Albregtsen
Jone Trovik
Gunnar B. Kristensen
Håvard E. Danielsen
Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
Cancers
chromatin compartments
chromatin organisation
texture analysis
prognostic marker
ovarian cancer
endometrial cancer
title Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
title_full Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
title_fullStr Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
title_full_unstemmed Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
title_short Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas
title_sort prognostic value of the diversity of nuclear chromatin compartments in gynaecological carcinomas
topic chromatin compartments
chromatin organisation
texture analysis
prognostic marker
ovarian cancer
endometrial cancer
url https://www.mdpi.com/2072-6694/12/12/3838
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