Deep Transfer Learning Links Benign Glands to Prostate Cancer Progression via Transcriptomics

The field effect describes the phenomena where environmental exposures, infection, and genetic predisposition result in molecular changes in cells that predispose them to developing cancer. Though this is a well-established concept in pathology, it remains underexplored in the context of high-resolution omics. We utilized the Diagnostic Evidence Gauge of Single Cells (DEGAS) deep transfer learning framework to analyze prostate cancer spatial transcriptomics to identify cells and tissues that are highly associated with cancer progression. DEGAS highlighted morphologically benign glands that had reduced expression of MSMB, a differentiation marker that is decreased in aggressive tumors. These glands have upregulated genes associated with antigen presentation and aggressive neoplasms. Integration of single-cell transcriptomics and deep learning image analysis separately revealed altered immune-cell infiltration, suggesting a complex interplay in the tumor environment facilitating aggressiveness. We used immunohistochemistry to quantify the MSMB protein (PSP-94) expression on morphologically normal and tumor tissues from patients with and without 5-year distant metastasis. Samples from patients who developed metastasis consistently showed lower fractions of positively stained cells, indicating a subtle yet significant "field effect" in seemingly benign regions. These proteomic results validate the transcriptomic findings and further underscore that inflammatory or immune-related changes in ostensibly normal tissue may contribute to aggressive disease progression.