Bartels Peter H, Montironi Rodolfo, Scarpelli Marina, Bartels Hubert G, Alberts David S
College of Optical Sciences and Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724-5024, USA.
Anal Quant Cytol Histol. 2009 Jun;31(3):125-36.
To present the rationale for applying different sequences of multivariate analysis algorithms to determine if and where, in the large and high-dimensional data space, events have led to change in karyometric features.
Clinical materials and results from the analysis of 4 studies were used: the demonstration of chemopreventive efficacy of letrozole in a situation where only a small subset of cells is affected, the detection of a preneoplastic lesion in colorectal tissue, data processing to document clues that predict risk of recurrence of a bladder lesion and the use of metafeatures and second-order discriminant analysis in a study of efficacy of vitamin A in the chemoprevention of skin lesions.
Evidence for chemopreventive efficacy was demonstrated in the first example only after processing identified the small subpopulation of affected nuclei in a study of breast epithelial cells. Detection of a preneoplastic development is linked to a progression curve connecting nuclei from normal tissue to nuclei from premalignant colorectal lesions. The prediction of risk of recurrence of papillary bladder lesions is possible by detecting changes in nuclei of a certain phenotype. Efficacy of vitamin A as a chemopreventive agent for skin cancer could be demonstrated with a dose-response curve after a second-order discriminant analysis was employed.
In none of these instances would the information of biologic interest have been revealed by a straightforward, single algorithmic analysis.
阐述应用不同多元分析算法序列的基本原理,以确定在大尺寸和高维度数据空间中,事件是否以及在何处导致了核测量特征的变化。
使用了4项研究的临床材料和分析结果:来曲唑在仅一小部分细胞受影响的情况下化学预防效果的论证、结直肠组织中癌前病变的检测、记录预测膀胱病变复发风险线索的数据处理,以及在维生素A化学预防皮肤病变疗效研究中使用元特征和二阶判别分析。
在第一项研究中,仅在处理确定了乳腺上皮细胞研究中受影响细胞核的小亚群后,才证明了化学预防效果的证据。癌前病变的检测与一条将正常组织细胞核与结直肠癌前病变细胞核连接起来的进展曲线相关。通过检测特定表型细胞核的变化,可以预测乳头状膀胱病变的复发风险。在采用二阶判别分析后,通过剂量反应曲线可以证明维生素A作为皮肤癌化学预防剂的疗效。
在这些情况中,通过直接的单一算法分析均无法揭示生物学相关信息。