spatiial gene expression analysis of a case with de novo NEPC and ARPC
Background: Neuroendocrine prostate carcinoma (NEPC) accounts for less than 1% of prostate neoplasms and has a very poor prognosis compared to the typical androgen receptor path-way-positive adenocarcinoma of the prostate (ARPC). Very few cases were reported in which de novo NEPC and APRC were diagnosed simultaneously in the same tissue. Objective: To analyze and report the differences in gene expression between de novo NEPC and ARPC using spatial gene expression analysis techniques. Design, setting, and participant: A single-case study of a 78-year-old man with non-muscle invasive urothelial carcinoma of the bladder conducted at Ehime University Hospital. Intervention: Robot-assisted laparoscopic cystoprostatectomy (RALC) was performed. Outcome measurements: Visium CytAssist Spatial Gene Expression analysis (10x genetics) was performed by Research Institute for Microbial Diseases at Osaka University. For-malin-fixed, paraffin-embedded (FFPE) samples passing the RNA quality control were used for sequencing. Results and limitations: The neuroendocrine signatures were upregulated in NEPC sites and androgen receptor signatures were upregulated in ARPC sites in prostate tissue. In ad-dition, no downregulation of TP53, RB1, or PTEN and upregulation of the HRR gene was observed at NEPC sites. No elevation of markers characteristic of urothelial carcinoma was observed. Furthermore, markers indicative of fibrosis were markedly elevated in the tumor microenvi-ronment surrounding the NEPC. Limitation is that this is only one case study, but it is very im-portant data that will lead to a better understanding of the genetic mechanism of de novo NEPC. Conclusions: The findings of spatial gene expression analysis in patients with coexisting ARPC and de novo NEPC are reported. Patient summary: The accumulation of cases and basic data will enable research and lead to the development of novel treatments for NEPC and improve the prognosis of patients with castration-resistant prostate cancer.