前列腺癌
转录组
肿瘤微环境
基因表达谱
癌症研究
生物
基因签名
人口
生化复发
生物标志物
疾病
前列腺
癌症
免疫系统
肿瘤科
医学
病理
免疫学
基因表达
基因
遗传学
环境卫生
前列腺切除术
作者
Paul Vinu Salachan,Martin Rasmussen,Benedicte Parm Ulhøi,Jørgen Bjerggaard Jensen,Michael Borre,Karina Dalsgaard Sørensen
摘要
Abstract Prostate cancer (PCa) is a highly heterogeneous disease in terms of its molecular makeup and clinical prognosis. The prostate tumor microenvironment (TME) is hypothesized to play an important role in driving disease aggressiveness, but precise mechanisms remain elusive. In our study, we used spatial transcriptomics to explore for the first time the spatial gene expression heterogeneity within primary prostate tumors from patients with metastatic disease. In total, we analyzed 5459 tissue spots from three PCa patients comprising castration‐resistant (CRPC) and neuroendocrine (NEPC) disease stages. Within CRPC, we identified a T cell cluster whose activity might be impaired by nearby regulatory T cells, potentially mediating the aggressive disease phenotype. Moreover, we identified Hallmark signatures of epithelial‐mesenchymal transition in a cancer‐associated fibroblast (CAF) cluster, indicating the aggressive characteristic of the primary TME leading to metastatic dissemination. Within NEPC, we identified active immune‐stroma cross‐talk exemplified by significant ligand‐receptor interactions between CAFs and M2 macrophages. Further, we identified a malignant cell population that was associated with the down‐regulation of an immune‐related gene signature. Lower expression of this signature was associated with higher levels of genomic instability in advanced PCa patients (SU2C cohort, n = 99) and poor recurrence free survival in early‐stage PCa patients (TCGA cohort, n = 395), suggesting prognostic biomarker potential. Taken together, our study reveals the importance of whole transcriptome profiling at spatial resolution for biomarker discovery and for advancing our understanding of tumor biology.
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