1. Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival.
- Author
-
Singhal SK, Byun JS, Park S, Yan T, Yancey R, Caban A, Hernandez SG, Hewitt SM, Boisvert H, Hennek S, Bobrow M, Ahmed MSU, White J, Yates C, Aukerman A, Vanguri R, Bareja R, Lenci R, Farré PL, De Siervi A, Nápoles AM, Vohra N, and Gardner K
- Subjects
- Automation, Laboratory, Breast Neoplasms genetics, Breast Neoplasms mortality, Breast Neoplasms pathology, Cell Line, Tumor, Female, Fluorescent Antibody Technique, Gene Expression Regulation, Neoplastic, Humans, Image Interpretation, Computer-Assisted, Microscopy, Fluorescence, Microtubule-Associated Proteins genetics, Prognosis, Retrospective Studies, Risk Assessment, Risk Factors, Signal Transduction, Time Factors, Tissue Array Analysis, Transcription Factors genetics, Tumor Escape, United States epidemiology, Breast Neoplasms metabolism, Microtubule-Associated Proteins metabolism, Transcription Factors metabolism, Tumor Microenvironment
- Abstract
The use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso's subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso's role in breast cancer progression.
- Published
- 2021
- Full Text
- View/download PDF