Centre de Recherche des Cordeliers, Université Paris Cité, Sorbonne Université, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France.
Mol Cancer. 2023 Aug 10;22(1):128. doi: 10.1186/s12943-023-01802-1.
Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis. Growing evidence suggests the association of PRC1 with multiple cancers. Here, we unveil that, in 28 cancer types, PRC1 is higher expressed in tumor tissues than in non-malignant tissues. Overexpression of PRC1 indicates unfavorable prognostic value, especially in ACC, LGG, KIRP, LICH, LUAD, MESO, PAAD, SARC and UCEC, while methylation of the PRC1 gene at sites associated with its inactivation has a favorable prognostic value in ACC, KIRP, LUAD, MESO, KIRP and LGG. Differentially expressed genes (DEGs) associated with high (> median) PRC1 expression contribute to key signaling pathways related with cell cycle, DNA damage and repair, EMT, cell migration, invasion and cell proliferation in most cancer types. More specifically, the DEGs involved in RAS/RAF/MAPK, PI3K/AKT, WNT, NOTCH, TGF-β, integrin, EMT process, focal adhesion, RHO GTPase-related pathway or microtubule cytoskeleton regulation are upregulated when PRC1 expression is above median, as confirmed for most cancers. Most importantly, high expression of PRC1 appears to be associated with an overabundance of poor-prognosis TH2 cells. Furthermore, positive correlations of PRC1 and some immune checkpoint genes (CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT, and CD86) were observed in several cancers, especially BLCA, BRCA, KIRC, LUAD, LIHC, PRAD and THCA. These findings plead in favor of further studies validating the diagnostic and prognostic impact of PRC1 as well as the elaboration of pharmacological strategies for targeting PRC1.
细胞分裂蛋白调节剂 1(PRC1)参与细胞分裂。越来越多的证据表明 PRC1 与多种癌症有关。在这里,我们揭示了在 28 种癌症类型中,PRC1 在肿瘤组织中的表达高于非恶性组织。PRC1 的过表达表明预后不良,特别是在 ACC、LGG、KIRP、LICH、LUAD、MESO、PAAD、SARC 和 UCEC 中,而 PRC1 基因与失活相关的位点的甲基化在 ACC、KIRP、LUAD、MESO、KIRP 和 LGG 中具有有利的预后价值。与高(>中位数)PRC1 表达相关的差异表达基因(DEGs)有助于与细胞周期、DNA 损伤和修复、EMT、细胞迁移、侵袭和细胞增殖相关的关键信号通路,在大多数癌症类型中都是如此。更具体地说,当 PRC1 表达高于中位数时,涉及 RAS/RAF/MAPK、PI3K/AKT、WNT、NOTCH、TGF-β、整合素、EMT 过程、焦点黏附、RHO GTPase 相关途径或微管细胞骨架调节的 DEGs 上调,这在大多数癌症中得到了证实。最重要的是,PRC1 的高表达似乎与预后不良的 TH2 细胞的过度产生有关。此外,在几种癌症中,观察到 PRC1 与一些免疫检查点基因(CD274、CTLA4、HAVCR2、LAG3、PDCD1、PDCD1LG2、TIGIT 和 CD86)之间存在正相关,特别是 BLCA、BRCA、KIRC、LUAD、LIHC、PRAD 和 THCA。这些发现支持进一步研究验证 PRC1 的诊断和预后影响,以及制定针对 PRC1 的药物治疗策略。