Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Biochem Genet. 2023 Aug;61(4):1369-1386. doi: 10.1007/s10528-022-10321-5. Epub 2023 Jan 4.
Increasing evidence has demonstrated that enhanced PHF20 expression plays a crucial role in cancer development and progression. However, little is known about the prognostic value of PHF20 expression in breast cancer (BRCA). In this study, we attempted to explore the expression pattern of PHF20 and its associations with prognosis and immune status in BRCA. The gene expression data and clinical information of 1109 BRCA samples were downloaded from TCGA database. The expression level of PHF20 protein was determined using UALCAN and HPA database. Kaplan-Meier method and CIBERSORT algorithm were used to analyze the associations of PHF20 expression with overall survival (OS) and immune microenvironment, respectively. Besides, GSEA analysis was conducted to explore potential biological functions and molecular mechanisms of PHF20 in BRCA. Moreover, starBase database was applied to construct a ceRNA nework. PHF20 was highly expressed in BRCA samples both at the transcriptional and protein level, and was strongly correlated with the OS and immune status. Univariable and multivariate Cox regression analyses identified PHF20 as an independent prognostic factor. Additionally, GSEA analysis showed that high PHF20 expression was closely associated with TGF-β signaling pathway, Wnt signaling pathway, and adherens junction. Furthermore, three ceRNA networks (AC037198.1/hsa-miR-223-3p/PHF20, CBR3-AS1/hsa-miR-223-3p/PHF20, and ZNF561-AS1/hsa-miR-223-3p/PHF20) were identified by starBase analysis. Functional experiments validated that PHF20 knockdown inhibited the cell viability and progression in BRCA cells. PHF20 overexpression was significantly associated with poor prognosis and immune status in BRCA, and could act as a potential novel prognostic biomarker for BRCA.
越来越多的证据表明，增强的 PHF20 表达在癌症的发生和发展中起着关键作用。然而，关于 PHF20 表达在乳腺癌（BRCA）中的预后价值知之甚少。在本研究中，我们试图探讨 PHF20 的表达模式及其与 BRCA 预后和免疫状态的关系。从 TCGA 数据库中下载了 1109 例 BRCA 样本的基因表达数据和临床信息。使用 UALCAN 和 HPA 数据库确定 PHF20 蛋白的表达水平。使用 Kaplan-Meier 方法和 CIBERSORT 算法分别分析 PHF20 表达与总生存期（OS）和免疫微环境的关系。此外，进行 GSEA 分析以探讨 PHF20 在 BRCA 中的潜在生物学功能和分子机制。此外，应用 starBase 数据库构建 ceRNA 网络。PHF20 在 BRCA 样本中的转录和蛋白水平均高度表达，与 OS 和免疫状态密切相关。单变量和多变量 Cox 回归分析确定 PHF20 是独立的预后因素。此外，GSEA 分析表明，高 PHF20 表达与 TGF-β 信号通路、Wnt 信号通路和黏着连接密切相关。此外，通过 starBase 分析鉴定了三个 ceRNA 网络（AC037198.1/hsa-miR-223-3p/PHF20、CBR3-AS1/hsa-miR-223-3p/PHF20 和 ZNF561-AS1/hsa-miR-223-3p/PHF20）。功能实验验证了 PHF20 敲低抑制了 BRCA 细胞的细胞活力和进展。PHF20 过表达与 BRCA 的不良预后和免疫状态显著相关，可作为 BRCA 的潜在新型预后生物标志物。
