Li Jiale, Wu Beiwen, Fan Guorui, Huang Jie, Li Zhiguo, Cao Fenghong
Clinical Medical College, North China University of Science and Technology, Tangshan, China.
The Hebei Key Lab for Organ Fibrosis, The Hebei Key Lab for Chronic Disease, School of Public Health, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, China.
PLoS One. 2024 Dec 23;19(12):e0314599. doi: 10.1371/journal.pone.0314599. eCollection 2024.
Chronic prostatitis may be a risk factor for developing proliferative changes in the prostate, although the underlying mechanisms are not entirely comprehended.
Fifty individual prostate tissues were examined in this study, consisting of 25 patients diagnosed with prostatic hyperplasia combined with histologic chronic inflammation and 25 patients diagnosed with prostatic hyperplasia alone. We employed UPLC-Q-TOF-MS-based untargeted metabolomics using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify differential metabolites that can reveal the mechanisms that underlie the promotion of prostate hyperplasia by histologic chronic inflammation. Selected differential endogenous metabolites were analyzed using bioinformatics and subjected to metabolic pathway studies.
Nineteen differential metabolites, consisting of nine up-regulated and ten down-regulated, were identified between the two groups of patients. These groups included individuals with combined histologic chronic inflammation and those with prostatic hyperplasia alone. Glycerolipids, glycerophospholipids, and sphingolipids were primarily the components present. Metabolic pathway enrichment was conducted on the identified differentially expressed metabolites. Topological pathway analysis revealed the differential metabolites' predominant involvement in sphingolipid, ether lipid, and glycerophospholipid metabolism. The metabolites involved in sphingolipid metabolism were Sphingosine, Cer (d18:1/24:1), and Phytosphingosine. The metabolites involved in ether lipid metabolism were Glycerophosphocholine and LysoPC (O-18:0/0:0). The metabolites involved in glycerophospholipid metabolism were LysoPC (P-18:0/0:0) and Glycerophosphocholine. with Impact > 0. 1 and FDR < 0. 05, the most important metabolic pathway was sphingolipid metabolism.
In conclusion, our findings suggest that patients with prostate hyperplasia and combined histologic chronic inflammation possess distinctive metabolic profiles. These differential metabolites appear to play a significant role in the pathogenesis of histologic chronic inflammation-induced prostate hyperplasia, primarily through the regulation of sphingolipids and glycerophospholipids metabolic pathways. The mechanism by which histologic chronic inflammation promotes prostate hyperplasia was elucidated through the analysis of small molecule metabolites. These findings support the notion that chronic prostatitis may contribute to an increased risk of prostate hyperplasia.
慢性前列腺炎可能是前列腺发生增生性改变的一个风险因素，尽管其潜在机制尚未完全明了。
本研究检测了50份个体前列腺组织，其中包括25例诊断为前列腺增生合并组织学慢性炎症的患者以及25例仅诊断为前列腺增生的患者。我们采用基于超高效液相色谱-四极杆飞行时间质谱联用（UPLC-Q-TOF-MS）的非靶向代谢组学方法，利用超高效液相色谱与四极杆飞行时间质谱联用技术来鉴定差异代谢物，这些差异代谢物能够揭示组织学慢性炎症促进前列腺增生的潜在机制。对选定的差异内源性代谢物进行生物信息学分析并开展代谢途径研究。
在两组患者之间鉴定出19种差异代谢物，其中9种上调，10种下调。这些组包括组织学慢性炎症合并前列腺增生的个体以及仅患有前列腺增生的个体。主要存在的成分包括甘油脂、甘油磷脂和鞘脂。对鉴定出的差异表达代谢物进行代谢途径富集分析。拓扑途径分析显示差异代谢物主要参与鞘脂、醚脂和甘油磷脂代谢。参与鞘脂代谢的代谢物有鞘氨醇、神经酰胺（d18:1/24:1）和植物鞘氨醇。参与醚脂代谢的代谢物有甘油磷酸胆碱和溶血磷脂酰胆碱（O-18:0/0:0）。参与甘油磷脂代谢的代谢物有溶血磷脂酰胆碱（P-18:0/0:0）和甘油磷酸胆碱。影响值>0.1且错误发现率<0.05时，最重要的代谢途径是鞘脂代谢。
总之，我们的研究结果表明，前列腺增生合并组织学慢性炎症的患者具有独特的代谢谱。这些差异代谢物似乎在组织学慢性炎症诱导的前列腺增生发病机制中发挥重要作用，主要通过调节鞘脂和甘油磷脂代谢途径。通过对小分子代谢物的分析阐明了组织学慢性炎症促进前列腺增生的机制。这些发现支持慢性前列腺炎可能导致前列腺增生风险增加这一观点。
