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.