Kaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival

Kaiso (ZBTB33) 亚细胞分区功能性地关联了 LC3A/B、肿瘤微环境和乳腺癌生存

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作者:Sandeep K Singhal #, Jung S Byun #, Samson Park, Tingfen Yan, Ryan Yancey, Ambar Caban, Sara Gil Hernandez, Stephen M Hewitt, Heike Boisvert, Stephanie Hennek, Mark Bobrow, Md Shakir Uddin Ahmed, Jason White, Clayton Yates, Andrew Aukerman, Rami Vanguri, Rohan Bareja, Romina Lenci, Paula Lucia Farré

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.

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