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In cancer research, supervised heterogeneity analysis has important implications. Such analysis has been traditionally based on clinical/demographic/molecular variables. Recently, histopathological imaging features, which are generated as a byproduct of biopsy, have been shown as effective for modeling cancer outcomes, and a handful of supervised heterogeneity analysis has been conducted based on such features. There are two types of histopathological imaging features, which are extracted based on specific biological knowledge and using automated imaging processing software, respectively. Using both types of histopathological imaging features, our goal is to conduct the first supervised cancer heterogeneity analysis that satisfies a hierarchical structure. That is, the first type of imaging features defines a rough structure, and the second type defines a nested and more refined structure. A penalization approach is developed, which has been motivated by but differs significantly from penalized fusion and sparse group penalization. It has satisfactory statistical and numerical properties. In the analysis of lung adenocarcinoma data, it identifies a heterogeneity structure significantly different from the alternatives and has satisfactory prediction and stability performance. [ABSTRACT FROM AUTHOR]

Heterogeneity is a hallmark of cancer. For various cancer outcomes/phenotypes, supervised heterogeneity analysis has been conducted, leading to a deeper understanding of disease biology and customized clinical decisions. In the literature, such analysis has been oftentimes based on demographic, clinical, and omics measurements. Recent studies have shown that high‐dimensional histopathological imaging features contain valuable information on cancer outcomes. However, comparatively, heterogeneity analysis based on imaging features has been very limited. In this article, we conduct supervised cancer heterogeneity analysis using histopathological imaging features. The penalized fusion technique, which has notable advantages—such as greater flexibility—over the finite mixture modeling and other techniques, is adopted. A sparse penalization is further imposed to accommodate high dimensionality and select relevant imaging features. To improve computational feasibility and generate more reliable estimation, we employ model averaging. Computational and statistical properties of the proposed approach are carefully investigated. Simulation demonstrates its favorable performance. The analysis of The Cancer Genome Atlas (TCGA) data may provide a new way of defining/examining breast cancer heterogeneity. [ABSTRACT FROM AUTHOR]

Histopathological imaging has been routinely conducted in cancer diagnosis and recently used for modeling other cancer outcomes/phenotypes such as prognosis. Clinical/environmental factors have long been extensively used in cancer modeling. However, there is still a lack of study exploring possible interactions of histopathological imaging features and clinical/environmental risk factors in cancer modeling. In this article, we explore such a possibility and conduct both marginal and joint interaction analysis. Novel statistical methods, which are "borrowed" from gene⁻environment interaction analysis, are employed. Analysis of The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) data is conducted. More specifically, we examine a biomarker of lung function as well as overall survival. Possible interaction effects are identified. Overall, this study can suggest an alternative way of cancer modeling that innovatively combines histopathological imaging and clinical/environmental data.