Abstract

Abstract Cancer evolution involves multiple stochastic processes across many scales. In addition to genomic and transcriptomic changes, hallmarks of cancer within solid tumors include the malignant co-evolution of the tumor microenvironment. Although the evaluation of tissue architecture plays a key role in pathologist staging, the automated extraction of additional structural features remains far from translation to the clinic. However, one particularly effective novel methodology for extracting patterns from these clinical images is topological data analysis(TDA). TDA is a field that studies the shape of data and its connectedness using concepts from geometric and algebraic topology. Recent work using topological data analysis has allowed the extraction of image features. Such features have been associated with clinical outcomes in both the analysis of H&E images in prostate cancer and CT images in lung cancer. We set out to question how the topological features of tissues, including tumor and stromal composition, evolve during treatment and between original sites and metastasis. To analyze this we use a combination of tissue sections, imaging, and cell-automata models and persistent homology and cubical persistence techniques from TDA. We apply certain topological methods for the first time to tissue images (H&E) and to the output of spatial simulations. We focus specifically on analyzing the evolution of topological features in ovarian and lung cancer and compare our features to 2D and 3D simulations (HAL) with varying game theoretical interactions as well as comparing features across tissues from matched primary and metastatic sites. We find that several topological features are conserved between primary and metastatic sites and some feature evolution is replicated in simulation. Citation Format: Rowan Barker-Clarke, Jason M. Gray, Jacob G. Scott. Topology of the tumor microenvironment: Integrating imaging, modeling, and topological data analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr PR016.

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