前列腺癌（PCa）是全世界男性中第二常见的恶性肿瘤。 PCa 的危险因素包括肥胖、年龄和家族史。内脏脂肪增加与前列腺癌高风险相关，这促使之前的研究人员研究身体成分和脂肪分布对前列腺癌预后的影响。然而，目前缺乏针对前列腺周围脂肪组织（PPAT）与 PCa 细胞之间机制和相互作用的研究。本研究调查了盆腔脂肪组织的组成与 PCa 侵袭性之间的关联，以了解该组织在 PCa 进展中所发挥的作用。此外，制备 PPAT 条件培养基 (CM) 以评估 PPAT 分泌组对 PCa 病理生理学的影响。本研究纳入了 50 名接受机器人辅助根治性前列腺切除术的局限性 PCa 患者。收集医疗记录、分析磁共振成像扫描并计算身体成分，以确定脂肪组织体积和临床 PCa 侵袭性之间的关联。此外，从手术期间收集的 25 名患者的 PPAT 和膀胱周围脂肪组织 (PVAT) 制备 CM，并研究其对 PCa 细胞系 C4-2 和 LNCaP 以及前列腺上皮细胞系 PZ-HPV-7 的影响使用细胞增殖测定和 RNA 测序 (RNA-seq)。结果显示，初始前列腺特异性抗原水平与盆腔和前列腺周围脂肪组织体积显着相关。此外，肿瘤扩展到囊外的患者的 PPAT 体积显着更高。与在对照和PVAT-CM中培养时相比，在PPAT-CM中培养细胞时PCa细胞增殖显着降低。 RNA-seq 显示，PPAT-CM 培养的细胞中免疫反应、细胞死亡和凋亡途径丰富，表明 PPAT-CM 分泌的细胞因子或其他因子诱导 PCa 细胞凋亡。这些发现表明，PPAT 分泌蛋白组可能通过激活免疫反应和促进癌细胞凋亡来抑制 PCa 细胞增殖。该机制可能在 PCa 的早期阶段充当一线防御。版权所有：© 2024 Shao 等人。

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.Copyright: © 2024 Shao et al.