Digital Pathology Uncovers Multi-Omic Hallmarks of Lung Cancer in Histopathology Images

• The hallmarks of cancer (HOC) describe the core characteristics and complexity underlying cancer progression. As our understanding of cancer has grown, the number of HOC has increased from six (1) to ten (2) to fourteen (3).

• While some HOC (e.g., inflammation and angiogenesis) can be visualized directly in pathological specimens such as cancer tissue, others are best understood via next-generation sequencing (NGS)-derived signatures. Given that most diagnostic, prognostic, and treatment decisions are made using pathology slides, there is a need to understand the relationship between hallmark-associated signatures and their presentation in the cancer tissue, including in the tumor microenvironment (TME).

• Digital pathology enables the quantification of tumor morphology, potentially revealing the underlying properties of a cancer. Conversely, the advent of pathology-based biomarkers necessitates linking morphological biomarkers to the conceptual scaffolding provided by cancer hallmarks.

• Here, we used a digital pathology approach to gain a deeper understanding of the relationships between the TME and HOC in non-small cell lung cancer (NSCLC).

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