Spatial transcriptomics of intraductal carcinoma of the prostate

Aims Intraductal carcinoma of the prostate (IDC‐P) is a strong indicator of poor prognosis in prostate cancer (PCa). We utilized the Visium Spatial Gene Expression platform to characterize the gene expression profiles and copy number variations (CNVs) of IDC‐P. Methods and Results Manually annotated IDC‐P components were relatively enriched in a single transcriptomic cluster identified by principal component analysis, which exhibited elevated expression of FOLH1 (PSMA), PSCA and PLA2G2A . Differential gene expression analysis between IDC‐P and non‐IDC‐P cancer tissues revealed up‐regulation of pathways related to chemotaxis and leukocyte migration, as well as gene sets associated with small cell lung carcinoma, suggesting a potential link to treatment‐related neuroendocrine prostate carcinoma. In contrast, non‐IDC‐P components showed increased expression of genes associated with extracellular matrix organization. InferCNV analysis identified distinct CNV patterns differentiating IDC‐P from non‐IDC‐P cancer components in four out of six cases. However, no common CNV alterations were shared across these cases, indicating molecular diversity among IDC‐P lesions. In the remaining cases, IDC‐P clustered with Gleason pattern 5 carcinoma, and no CNV alterations distinguishing IDC‐P from adjacent non‐IDC‐P components were identified. Conclusions These findings suggest that IDC‐P represents a biologically distinct component from conventional acinar adenocarcinoma and may reflect spatial tumour progression through pre‐existing ductal structures. Our study also suggests that the molecular mechanisms underlying IDC‐P progression may differ between patients, while the limited sample size ( n = 6) warrants cautious interpretation and further validation in larger cohorts.