Elucidating the recurrence mechanisms of adamantinomatous craniopharyngioma by integrating single-cell and spatial transcriptomics analyses

Recurrence of adamantinomatous craniopharyngioma (ACP) is relatively common in clinical practice, yet the mechanisms underlying its recurrence remain poorly understood. Here, we performed spatial transcriptome sequencing analysis on paired formalin-fixed paraffin-embedded (FFPE) samples of primary and recurrent ACP from the same patient to construct spatial cellular maps of ACP in primary and recurrent states. Additionally, we utilized single-cell sequencing technology to conduct transcriptome analysis on fresh primary and recurrent samples to delineate their cellular and tumour microenvironment landscapes. Integrative analysis of these datasets enabled us to group common cell populations into clusters and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes in each cell population between primary and recurrent samples. We observed a significantly increased proportion of regulatory T (Treg) cells in recurrent samples. In macrophages, IL-4R expression was markedly elevated in recurrent samples, indicating enhanced M2 polarisation. Further analysis of immune cells revealed significantly elevated SRGN expression in recurrent samples and activation of the SPP1-CD44 cell communication pathway. These findings suggest that Treg cells, IL-4/IL-4R signalling, SRGN and SPP1-CD44 pathways are interconnected and collectively promote ACP recurrence. Our study delineates the spatial cellular maps of primary and recurrent ACP samples, uncovering potential mechanisms of recurrence. Moreover, we propose that SRGN may serve as a biomarker for predicting recurrence, and identify SPP1-CD44 as a candidate clinical therapeutic target for ACP.