研究动态
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剖析前列腺癌:单细胞洞察巨噬细胞多样性、分子预测因子以及肽基脯氨酰异构酶 F 的作用。

Dissecting prostate Cancer: Single-Cell insight into Macrophage Diversity, molecular Prognosticators, and the role of Peptidylprolyl Isomerase F.

发表日期:2024 Jul 02
作者: Bo Guan, Cong Huang, Libing Meng, Shangrong Zhang, Qing Liu, Xiaowei Wang, Xiaowei Li, Zongyao Hao
来源: Cellular & Molecular Immunology

摘要:

前列腺癌仍然是肿瘤学中的一个突出挑战,晚期前列腺癌预后较差。肿瘤微环境(TME),特别是肿瘤相关巨噬细胞(TAM),在疾病进展中发挥着至关重要的作用。本研究探索前列腺癌的单细胞转录组学,确定巨噬细胞异质性,鉴定预后基因标记,并评估 PPIF 在 TAM 中的作用。来自 GEO 数据库 (GSE176031) 的单细胞 RNA 测序数据和来自 TCGA 的转录组数据进行处理以表征细胞群并鉴定前列腺癌的预后基因。通过聚类检查巨噬细胞亚群,然后根据迁移、激活和增殖进行基因集评分。使用多重免疫荧光染色对匹配的前列腺癌和邻近非肿瘤组织进行巨噬细胞中 PPIF 表达的研究。单细胞分析鉴定了 9,178 个细胞,分为 10 种主​​要细胞类型,其中巨噬细胞构成了免疫微环境的重要组成部分。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。总共鉴定出 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 TAM 中肽基脯氨酰异构酶 F (PPIF) 的表达显着高于正常组织,表明其在免疫微环境中的潜在调节作用。前列腺癌 TME 复杂的细胞结构已被阐明,重点关注巨噬细胞异质性和功能性。专业化。包括 PPIF 在内的预后基因与生存结果相关,提供了潜在的治疗靶点。 PPIF 在 TAM 中的显着表达可能会成为癌症进展的杠杆,值得进一步研究作为前列腺癌环境中治疗靶向的生物标志物和感兴趣的分子。版权所有 © 2024 Elsevier B.V. 保留所有权利。
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.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.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.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.Copyright © 2024 Elsevier B.V. All rights reserved.