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Abstract Perineural invasion (PNI), or the invasion of cancer to the space surrounding nerves, is associated with poor prognosis, but the underlying molecular factors that drive its initiation and progression are poorly understood. To explore this systematically, we applied a 6000-plex spatial transcriptomic panel with subcellular resolution to curated microarrays from 5 pancreatic ductal adenocarcinoma (PDAC) patients spanning different stages of tumor-nerve involvement. With this preliminary cohort, we explored malignant cell signatures associated with invasion and adaptation to the intraneural environment. Strikingly, we observed enrichment of a classical-like malignant transcriptional program marked by genes involved in glucose and lipid metabolism in nerve-invading malignant cells. Despite the known association of chemoresistance with serine dependence, these cells also exhibited upregulation of genes involved in serine biosynthesis, suggesting that intraneural invasion may offer an orthogonal path of treatment evasion. Overall, our findings indicate that nerve-invasive cancer cells adopt a unique transcriptomic signature within the neuronal microenvironment. Further studies will aim to uncover the relevance of these signatures to survival within the nerve environment and treatment resistance. Citation Format: Deniz Guney Olgun, Peter L. Wang, Ryan Zhao, Dennis H. Gong, William L. Hwang. High-resolution spatial transcriptomics identifies candidate genes facilitating perineural invasion abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 4901.
Olgun et al. (Fri,) studied this question.