Unveiling the Genomic Landscape of Intraductal Carcinoma of the Prostate Using Spatial Gene Expression Analysis

Abstract

Intraductal carcinoma of the prostate (IDCP) has recently attracted increasing interest owing to its unfavorable prognoses. To effectively identify the IDCP-specific gene expression profile, we took a novel approach of characterizing a typical IDCP case using spatial gene expression analysis. A formalin-fixed, paraffin-embedded sample was subjected to Visium CytAssist Spatial Gene Expression analysis. IDCP within invasive prostate cancer sites was recognized as a distinct cluster separate from other invasive cancer clusters. Highly expressed genes defining the IDCP cluster, such as <i>MUC6</i>, <i>MYO16</i>, <i>NPY</i>, and <i>KLK12</i>, reflected the aggressive nature of high-grade prostate cancer. IDCP sites also showed increased hypoxia markers <i>HIF1A</i>, <i>BNIP3L</i>, <i>PDK1</i>, and <i>POGLUT1</i>; decreased fibroblast markers <i>COL1A2</i>, <i>DCN</i>, and <i>LUM</i>; and decreased immune cell markers <i>CCR5</i> and <i>FCGR3A</i>. Overall, these findings indicate that the hypoxic tumor microenvironment and reduced recruitment of fibroblasts and immune cells, which reflect morphological features of IDCP, may influence the aggressiveness of high-grade prostate cancer.