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Open AccessArticle

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

1
Institute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424 Oslo, Norway
2
Department of Informatics, University of Oslo, NO-0316 Oslo, Norway
3
Department of Obstetrics and Gynecology, Haukeland University Hospital, NO-5020 Bergen, Norway
4
Department of Clinical Science, University of Bergen, NO-5020 Bergen, Norway
5
Department of Gynecologic Oncology, Oslo University Hospital, NO-0424 Oslo, Norway
6
Institute of Clinical Medicine, University of Oslo, NO-0318 Oslo, Norway
7
Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9DU, UK
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(12), 3838; https://doi.org/10.3390/cancers12123838
Received: 26 November 2020 / Revised: 15 December 2020 / Accepted: 16 December 2020 / Published: 19 December 2020
(This article belongs to the Special Issue Nuclear Architecture in Cancer)
Chromatin organisation affects gene expression and contributes to carcinogenesis. Automatic quantification of chromatin heterogeneity can be applied to identify patients with increased risk of cancer recurrence and death in several cancer types. We aimed to investigate the prognostic role of diversity of chromatin compartments in relation to chromatin heterogeneity and as a potential supplement to pathological risk classifications in gynaecological carcinomas. To this end, we computed the entropy of both chromatin compartment sizes and optical densities within compartments. In analysis of two cohorts consisting of 1037 patients with gynaecological carcinoma, we observed a moderately strong correlation between the prognostic value of the entropies and chromatin heterogeneity. The entropies provided an objective marker, which, integrated with pathological risk classifications, might possibly contribute to the selection of high-risk stage I ovarian carcinoma patients for adjuvant chemotherapy and to preoperative identification of low-risk endometrial carcinoma patients who are candidates for less extensive surgery.
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 (r 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. View Full-Text
Keywords: chromatin compartments; chromatin organisation; texture analysis; prognostic marker; ovarian cancer; endometrial cancer chromatin compartments; chromatin organisation; texture analysis; prognostic marker; ovarian cancer; endometrial cancer
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MDPI and ACS Style

Kleppe, A.; Albregtsen, F.; Trovik, J.; Kristensen, G.B.; Danielsen, H.E. Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas. Cancers 2020, 12, 3838. https://doi.org/10.3390/cancers12123838

AMA Style

Kleppe A, Albregtsen F, Trovik J, Kristensen GB, Danielsen HE. Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas. Cancers. 2020; 12(12):3838. https://doi.org/10.3390/cancers12123838

Chicago/Turabian Style

Kleppe, Andreas; Albregtsen, Fritz; Trovik, Jone; Kristensen, Gunnar B.; Danielsen, Håvard E. 2020. "Prognostic Value of the Diversity of Nuclear Chromatin Compartments in Gynaecological Carcinomas" Cancers 12, no. 12: 3838. https://doi.org/10.3390/cancers12123838

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