PRDM5 低表达预示着食管鳞癌预后不良。
Low expression of PRDM5 predicts poor prognosis of esophageal squamous cell carcinoma.
机构信息
Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu, China.
Cancer Research Center Nantong, Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu, China.
出版信息
BMC Cancer. 2022 Jul 7;22(1):745. doi: 10.1186/s12885-022-09787-8.
BACKGROUND
The role of the PRDM5 in esophageal squamous cell carcinoma (ESCC) has not been revealed. This study investigated the relationship between PRDM5 expression and survival outcome in esophageal squamous cell carcinoma and explored the mechanism in tumor development.
METHODS
In present study, expression of PRDM5 mRNA in esophageal squamous cell carcinoma patients was conducted using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. The expression of PRDM5 was assessed by immunohistochemical staining. Kaplan-Meier curve and Cox regression analysis was performed to analyze the survival outcome and independent predictive factors. qRT-PCR and Methylation-specific PCR were performed to identify the mRNA level of PRDM5 and Methylation rate. Cibersort algorithm to analyze the relationship between PRDM5 expression and immune cell invasion. Western-blot was performed to confirm the expression of esophageal tumor tissues and adjacent tissues.
RESULTS
The TCGA database and GEO database show that PRDM5 mRNA level in esophageal squamous cell carcinoma adjacent tissues was higher than that of cancer tissues, and ESCC patients with high expression of PRDM5 mRNA had better overall survival. Tissue microarray showed that the protein level of PRDM5 in the adjacent tissues of patients with ESCC was higher than that in cancer tissues, and the expression level of PRDM5 was significantly correlated with the grade of clinicopathological characteristics (P < 0.001). Patients with high expression of PRDM5 displayed a better OS and DFS. Cox regression analysis showed that PRDM5 was an independent risk factor and prognostic factor for ESCC patients (HR: 2.626, 95%CI: 1.824-3.781; P < 0.001). The protein level of PRDM5 matched with the transcriptional level, whereas the DNA methylation affected the transcriptional level. Cibersort showed that T cells CD4 memory resting, mast cells resting, eosinophils, M2 macrophages and mast cells activated were significantly positively correlated with PRDM5 expression (P < 0.05), while regulatory T cells, monocytes and dendritic cells negatively correlated with PRDM5 expression (P < 0.05).
CONCLUSION
PRDM5 can be used as a biomarker to predict the survival of ESCC patients. Furthermore, PRDM5 expression in ESCC cells may affect WNT/β-catenin signaling pathways, thus further affect the ESCC cell proliferation, migration, and invasion capacity.
背景
PRDM5 在食管鳞状细胞癌（ESCC）中的作用尚未被揭示。本研究旨在探讨 PRDM5 表达与 ESCC 患者生存结局的关系，并探索其在肿瘤发生发展中的机制。
方法
本研究采用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据库检测食管鳞状细胞癌患者 PRDM5 mRNA 的表达。采用免疫组织化学染色法检测 PRDM5 的表达。采用 Kaplan-Meier 曲线和 Cox 回归分析评估生存结局和独立预测因素。采用 qRT-PCR 和甲基化特异性 PCR 鉴定 PRDM5 的 mRNA 水平和甲基化率。采用 Cibersort 算法分析 PRDM5 表达与免疫细胞浸润的关系。采用 Western-blot 验证食管肿瘤组织及其邻近组织中 PRDM5 的表达。
结果
TCGA 数据库和 GEO 数据库显示，食管鳞状细胞癌邻近组织中 PRDM5 mRNA 水平高于癌组织，且 PRDM5 mRNA 高表达的 ESCC 患者总生存时间更好。组织微阵列分析显示，ESCC 患者癌旁组织中 PRDM5 蛋白水平高于癌组织，且 PRDM5 表达水平与临床病理特征分级显著相关（P<0.001）。PRDM5 高表达患者的 OS 和 DFS 更好。Cox 回归分析显示，PRDM5 是 ESCC 患者的独立预后危险因素（HR：2.626，95%CI：1.824-3.781；P<0.001）。PRDM5 的蛋白水平与转录水平相匹配，而 DNA 甲基化影响转录水平。Cibersort 分析显示，CD4 记忆静息 T 细胞、静止肥大细胞、嗜酸性粒细胞、M2 巨噬细胞和激活肥大细胞与 PRDM5 表达呈显著正相关（P<0.05），而调节性 T 细胞、单核细胞和树突状细胞与 PRDM5 表达呈显著负相关（P<0.05）。
结论
PRDM5 可作为预测 ESCC 患者生存的生物标志物。此外，ESCC 细胞中 PRDM5 的表达可能影响 WNT/β-catenin 信号通路，从而进一步影响 ESCC 细胞的增殖、迁移和侵袭能力。
Zotero 插件