Development of a nuclear morphometric signature for prostate cancer risk in negative biopsies.
Development of a nuclear morphometric signature for prostate cancer risk in negative biopsies.
复制标题
DOI：
10.1371/journal.pone.0069457
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ananthanarayanan V
中科院分区：
文献类型：
--
作者：
Gann PH;Deaton R;Amatya A;Mohnani M;Rueter EE;Yang Y;Ananthanarayanan V
我们的目标是开发和验证基于直接DNA染色图像分析的多特征核评分，并测试其与良性活检中前列腺癌（PCa）的场效应和后续检测的相关性。对来自39例切除术的组织切片进行Feulgen染色和数字扫描（400×），提供每个像素的DNA含量图。PCa和良性上皮细胞核被随机选择用于测量52个基本形态计量学特征。建立区分良性与PCa核以及良性与恶性核群体的逻辑回归模型，并通过AUC分析进行交叉验证。从<1 mm or >癌灶和无癌前列腺、HGPIN和Gleason 3-5级PCa中随机收集5 mm的细胞核群。还从随后诊断为PCa的阴性活检受试者和年龄匹配的无癌症对照（20对）中收集细胞核。在训练和验证患者集中，多特征核评分分别以0.91和0.79的AUC区分癌症和良性细胞群。在前列腺切除术样本中，核水平和群体水平模型均显示与前列腺癌相邻的良性核具有癌样特征，而与前列腺癌较远或来自无前列腺癌腺体的核相比。在阴性活检中，具有5个方差特征的经验证的模型在病例中的得分显著高于对照组（P = 0.026）。 通过自动数字分析获得的多特征核形态测量评分被验证用于区分良性和癌细胞核。该评分表明，在距PCa病变不同距离的良性上皮细胞核中存在场效应，并且与随后在阴性活检中检测到的PCa相关。该核评分显示有希望作为活检阴性男性的风险预测因子，并作为II期化学预防试验的中间生物标志物。结果还表明，核结构的亚视障碍先于肿瘤前病变的发展。
Our objective was to develop and validate a multi-feature nuclear score based on image analysis of direct DNA staining, and to test its association with field effects and subsequent detection of prostate cancer (PCa) in benign biopsies. Tissue sections from 39 prostatectomies were Feulgen-stained and digitally scanned (400×), providing maps of DNA content per pixel. PCa and benign epithelial nuclei were randomly selected for measurement of 52 basic morphometric features. Logistic regression models discriminating benign from PCa nuclei, and benign from malignant nuclear populations, were built and cross-validated by AUC analysis. Nuclear populations were randomly collected <1 mm or >5 mm from cancer foci, and from cancer-free prostates, HGPIN, and PCa Gleason grade 3–5. Nuclei also were collected from negative biopsy subjects who had a subsequent diagnosis of PCa and age-matched cancer-free controls (20 pairs). A multi-feature nuclear score discriminated cancer from benign cell populations with AUCs of 0.91 and 0.79, respectively, in training and validation sets of patients. In prostatectomy samples, both nuclear- and population-level models revealed cancer-like features in benign nuclei adjacent to PCa, compared to nuclei that were more distant or from PCa-free glands. In negative biopsies, a validated model with 5 variance features yielded significantly higher scores in cases than controls (P = 0.026). A multifeature nuclear morphometric score, obtained by automated digital analysis, was validated for discrimination of benign from cancer nuclei. This score demonstrated field effects in benign epithelial nuclei at varying distance from PCa lesions, and was associated with subsequent PCa detection in negative biopsies. This nuclear score shows promise as a risk predictor among men with negative biopsies and as an intermediate biomarker in Phase II chemoprevention trials. The results also suggest that subvisual disturbances in nuclear structure precede the development of pre-neoplastic lesions.
登录
查看更多内容
影响因子：
23.4
作者：
Montironi, R;Hamilton, PW;Bartels, PH
通讯作者：
Bartels, PH
影响因子：
4.5
作者：
Mohamed, Mahmoud A.;Greif, Philipp A.;Hamilton, Peter W.
通讯作者：
Hamilton, Peter W.
影响因子：
2.8
作者：
Ellinger, Joerg;Kahl, Philip;von Ruecker, Alexander
通讯作者：
von Ruecker, Alexander
影响因子：
2.1
作者：
Boone, CW;Lieberman, R;Bartels, P
通讯作者：
Bartels, P
影响因子：
3.8
作者：
Frank, Denise H.;Kimler, Bruce F.;Bartels, Peter H.
通讯作者：
Bartels, Peter H.