Kleppe Andreas, Albregtsen Fritz, Trovik Jone, Kristensen Gunnar B, Danielsen Håvard E
Institute for Cancer Genetics and Informatics, Oslo University Hospital, NO-0424 Oslo, Norway.
Department of Informatics, University of Oslo, NO-0316 Oslo, Norway.
Cancers (Basel). 2020 Dec 19;12(12):3838. doi: 10.3390/cancers12123838.
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 ( 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.
对经DNA染色的癌细胞核进行统计纹理分析，最近已被用于开发一种染色质异质性的泛癌预后标志物。在本研究中，我们转而通过自动量化癌细胞核中染色质区室的多样性来分析染色质组织。目的是研究这种评估在染色质异质性方面的预后价值，以及作为妇科癌症病理风险分类的潜在补充。通过计算染色质区室大小和区内光密度的熵来量化多样性。我们分析了246例卵巢癌患者的281个细胞核（四分位间距（IQR），273至289）的中位数，以及791例子宫内膜癌患者的997个细胞核（IQR，502至1452）的中位数。熵与染色质异质性的预后价值呈中度强相关（范围为0.68至0.73），但观察到这种新标志物可提供额外的预后信息。在与临床和病理标志物的多变量分析中，卵巢癌中与新标志物相关的风险比为2.1（95%CI，1.3至3.5），子宫内膜癌中为2.4（95%CI，1.5至3.9）。与病理风险分类相结合产生了三个预后明显不同的风险组。这表明染色质区室多样性的新标志物可能有助于选择高危I期卵巢癌患者进行辅助化疗，以及低危子宫内膜癌患者进行范围较小的手术。
