关键词: Apoptosis Gastric cancer NANOG PRDM14 Prognostic model

Mesh : Stomach Neoplasms / genetics pathology drug therapy metabolism Humans Transcription Factors / genetics metabolism DNA-Binding Proteins / genetics metabolism Prognosis Cell Line, Tumor Gene Expression Regulation, Neoplastic RNA-Binding Proteins / genetics metabolism Female Male Nomograms Apoptosis Biomarkers, Tumor / genetics metabolism Cell Proliferation Epigenesis, Genetic

来  源:   DOI:10.1186/s12885-024-12424-1   PDF(Pubmed)

Abstract:
BACKGROUND: Gastric cancer is one of the most common tumors worldwide, and most patients are deprived of treatment options when diagnosed at advanced stages. PRDM14 has carcinogenic potential in breast and non-small cell lung cancer. however, its role in gastric cancer has not been elucidated.
METHODS: We aimed to elucidate the expression of PRDM14 using pan-cancer analysis. We monitored the expression of PRDM14 in cells and patients using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. We observed that cell phenotypes and regulatory genes were influenced by PRDM14 by silencing PRDM14. We evaluated and validated the value of the PRDM14-derived prognostic model. Finally, we predicted the relationship between PRDM14 and small-molecule drug responses using the Connectivity Map and The Genomics of Drug Sensitivity in Cancer databases.
RESULTS: PRDM14 was significantly overexpressed in gastric cancer, which identified in cell lines and patients\' tissues. Silencing the expression of PRDM14 resulted in apoptosis promotion, cell cycle arrest, and inhibition of the growth and migration of GC cells. Functional analysis revealed that PRDM14 acts in epigenetic regulation and modulates multiple DNA methyltransferases or transcription factors. The PRDM14-derived differentially expressed gene prognostic model was validated to reliably predict the patient prognosis. Nomograms (age, sex, and PRDM14-risk score) were used to quantify the probability of survival. PRDM14 was positively correlated with sensitivity to small-molecule drugs such as TPCA-1, PF-56,227, mirin, and linsitinib.
CONCLUSIONS: Collectively, our findings suggest that PRDM14 is a positive regulator of gastric cancer progression. Therefore, it may be a potential therapeutic target for gastric cancer.
摘要:
背景:胃癌是全球最常见的肿瘤之一,大多数患者在晚期诊断时被剥夺了治疗选择。PRDM14在乳腺癌和非小细胞肺癌中具有致癌潜力。然而,其在胃癌中的作用尚未阐明。
方法:我们旨在使用泛癌症分析阐明PRDM14的表达。我们使用定量聚合酶链反应监测细胞和患者中PRDM14的表达,西方印迹,和免疫组织化学。我们观察到细胞表型和调节基因通过沉默PRDM14受到PRDM14的影响。我们评估并验证了PRDM14衍生的预后模型的价值。最后,我们使用癌症数据库中的ConnectivityMap和药物敏感性基因组学预测了PRDM14与小分子药物应答之间的关系.
结果:PRDM14在胃癌中显著过表达,在细胞系和患者组织中鉴定。沉默PRDM14的表达导致细胞凋亡的促进,细胞周期停滞,抑制GC细胞的生长和迁移。功能分析显示,PRDM14在表观遗传调控中起作用,并调节多种DNA甲基转移酶或转录因子。PRDM14衍生的差异表达基因预后模型被验证以可靠地预测患者预后。列线图(年龄,性别,和PRDM14风险评分)用于量化生存概率。PRDM14与TPCA-1、PF-56,227、mirin、还有linsitinib.
结论:总的来说,我们的发现提示PRDM14是胃癌进展的正调控因子.因此,它可能是胃癌的潜在治疗靶点。
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