Abstract：
BACKGROUND: Prostate cancer remains a prominent challenge in oncology, with advanced stages showing poor prognosis. The tumor microenvironment (TME), and particularly tumor-associated macrophages (TAMs), plays a crucial role in disease progression. This study explores the single-cell transcriptomics of prostate cancer, determines macrophage heterogeneity, identifies prognostic gene markers, and assesses the role of PPIF in TAMs.
METHODS: Single-cell RNA sequencing data from the GEO database (GSE176031) and transcriptome data from the TCGA were processed to characterize cell populations and identify prognostic genes in prostate cancer. Macrophage subpopulations were examined through clustering, followed by gene set scoring based on migration, activation, and proliferation. PPIF expression in macrophages was investigated using multiplex immunofluorescence staining on matched prostate cancer and adjacent non-tumoral tissues.
RESULTS: The single-cell analysis identified 9,178 cells, categorized into 10 principal cell types, with macrophages constituting a significant part of the immune microenvironment. Four macrophage subgroups demonstrated distinct functional pathways: phagocytic, immune-regulatory, and proliferative. A total of 39 genes correlated with prostate cancer prognosis were identified, of which 10 carried the most significant prognostic information. Peptidylprolyl Isomerase F (PPIF) expression was significantly higher in TAMs from tumor tissue than normal tissue, indicating its potential regulatory role in the immune microenvironment.
CONCLUSIONS: The intricate cellular architecture of the prostate cancer TME has been elucidated, with a focus on macrophage heterogeneity and functional specialization. Prognostic genes, including PPIF, were associated with survival outcomes, providing potential therapeutic targets. PPIF\'s prominent expression in TAMs may serve as a lever in cancer progression, warranting further investigation as a biomarker and a molecule of interest for therapeutic targeting within the prostate cancer milieu.
METHODS: Single-cell RNA sequencing data from the GEO database (GSE176031) and transcriptome data from the TCGA were processed to characterize cell populations and identify prognostic genes in prostate cancer. Macrophage subpopulations were examined through clustering, followed by gene set scoring based on migration, activation, and proliferation. PPIF expression in macrophages was investigated using multiplex immunofluorescence staining on matched prostate cancer and adjacent non-tumoral tissues.
RESULTS: The single-cell analysis identified 9,178 cells, categorized into 10 principal cell types, with macrophages constituting a significant part of the immune microenvironment. Four macrophage subgroups demonstrated distinct functional pathways: phagocytic, immune-regulatory, and proliferative. A total of 39 genes correlated with prostate cancer prognosis were identified, of which 10 carried the most significant prognostic information. Peptidylprolyl Isomerase F (PPIF) expression was significantly higher in TAMs from tumor tissue than normal tissue, indicating its potential regulatory role in the immune microenvironment.
CONCLUSIONS: The intricate cellular architecture of the prostate cancer TME has been elucidated, with a focus on macrophage heterogeneity and functional specialization. Prognostic genes, including PPIF, were associated with survival outcomes, providing potential therapeutic targets. PPIF\'s prominent expression in TAMs may serve as a lever in cancer progression, warranting further investigation as a biomarker and a molecule of interest for therapeutic targeting within the prostate cancer milieu.
摘要：
背景：前列腺癌仍然是肿瘤学的一个突出挑战，晚期显示预后不良。肿瘤微环境（TME），特别是肿瘤相关巨噬细胞（TAMs），在疾病进展中起着至关重要的作用。这项研究探讨了前列腺癌的单细胞转录组学，决定了巨噬细胞的异质性，确定预后基因标记，
方法：处理来自GEO数据库（GSE176031）的单细胞RNA测序数据和来自TCGA的转录组数据，以表征细胞群体并鉴定前列腺癌的预后基因。巨噬细胞亚群通过聚类检查，然后是基于迁移的基因集评分，激活,和扩散。在匹配的前列腺癌和邻近的非肿瘤组织上使用多重免疫荧光染色研究巨噬细胞中的PPIF表达。
结果：单细胞分析确定了9,178个细胞，分为10种主要细胞类型，巨噬细胞构成免疫微环境的重要部分。四个巨噬细胞亚群表现出不同的功能途径：吞噬，免疫调节，和增殖。共鉴定出39个与前列腺癌预后相关的基因。其中10个携带最重要的预后信息。肿瘤组织TAMs中的肽基丙氨酰基异构酶F(PPIF)表达明显高于正常组织,表明其在免疫微环境中的潜在调节作用。
结论：已经阐明了前列腺癌TME的复杂细胞结构，重点关注巨噬细胞异质性和功能特化。预后基因，包括PPIF，与生存结果相关，提供潜在的治疗靶点。PPIF在TAM中的突出表达可能是癌症进展的杠杆，保证进一步研究作为生物标志物和感兴趣的分子用于前列腺癌环境中的治疗靶向。
方法：处理来自GEO数据库（GSE176031）的单细胞RNA测序数据和来自TCGA的转录组数据，以表征细胞群体并鉴定前列腺癌的预后基因。巨噬细胞亚群通过聚类检查，然后是基于迁移的基因集评分，激活,和扩散。在匹配的前列腺癌和邻近的非肿瘤组织上使用多重免疫荧光染色研究巨噬细胞中的PPIF表达。
结果：单细胞分析确定了9,178个细胞，分为10种主要细胞类型，巨噬细胞构成免疫微环境的重要部分。四个巨噬细胞亚群表现出不同的功能途径：吞噬，免疫调节，和增殖。共鉴定出39个与前列腺癌预后相关的基因。其中10个携带最重要的预后信息。肿瘤组织TAMs中的肽基丙氨酰基异构酶F(PPIF)表达明显高于正常组织,表明其在免疫微环境中的潜在调节作用。
结论：已经阐明了前列腺癌TME的复杂细胞结构，重点关注巨噬细胞异质性和功能特化。预后基因，包括PPIF，与生存结果相关，提供潜在的治疗靶点。PPIF在TAM中的突出表达可能是癌症进展的杠杆，保证进一步研究作为生物标志物和感兴趣的分子用于前列腺癌环境中的治疗靶向。
