PDF(Pubmed)
Abstract：
BACKGROUND: The early diagnosis of gastric cancer (GC) and overcoming chemotherapy resistance is challenging. The aberrant expression of zinc finger protein 281 (ZNF281) and the over-activation of the Wnt/β-catenin pathway are oncogenic factors and confer tumor chemoresistance. ZNF281 modulates the Wnt/β-catenin pathway to influence malignant tumor behavior. However, the role of ZNF281 in GC chemotherapy and the relationship with the Wnt/β-catenin pathway have not been elucidated by researchers.
METHODS: We explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281\'s role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/β-catenin pathway proteins.
RESULTS: ZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/β-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells.
CONCLUSIONS: We identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/β-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.
METHODS: We explored differences in ZNF281 expression in Pan-cancer and normal tissues, the effect of its expression on prognosis of patients treated with 5-fluorouracil (5-FU). Cox regression was utilized to determine whether ZNF281 is an independent prognostic factor. Enrichment analysis was performed to explore the mechanism underlying ZNF281\'s role in 5-FU treatment. We assessed the relationship between ZNF281 and the tumour microenvironment (TME) and combined bulk-RNA and single-cell RNA data to analyse the relationship between ZNF281 and immune infiltration. In vitro experiments verified the effects of ZNF281 knockdown on proliferation, invasion, migration, apoptosis, DNA damage of GC cells with 5-FU treated and the Wnt/β-catenin pathway proteins.
RESULTS: ZNF281 was highly expressed in seven cancers and correlates with the prognosis. It is an independent prognostic factor in 5-FU treatment. ZNF281 correlates with TME score, CD8T cell abundance. ZNF281 is primarily associated with DNA repair and the Wnt/β-catenin pathway. ZNF281 knockdown enhanced the effect of 5-FU on phenotypes of GC cells.
CONCLUSIONS: We identified and verified ZNF281 as one of the potential influencing factors of 5-FU treatment in GC and may be associated with the Wnt/β-catenin pathway. Low ZNF281 may contribute to improved 5-FU sensitivity in GC patients.
摘要：
背景：胃癌（GC）的早期诊断和克服化疗耐药性具有挑战性。锌指蛋白281（ZNF281）的异常表达和Wnt/β-catenin途径的过度激活是致癌因素，并赋予肿瘤化学抗性。ZNF281调节Wnt/β-catenin通路影响恶性肿瘤行为。然而,研究人员尚未阐明ZNF281在GC化疗中的作用以及与Wnt/β-catenin通路的关系。
方法：我们探索了ZNF281在泛癌和正常组织中的表达差异，其表达对5-氟尿嘧啶（5-FU）治疗患者预后的影响。Cox回归分析用于确定ZNF281是否是独立的预后因素。进行富集分析以探讨ZNF281在5-FU治疗中的作用机制。我们评估了ZNF281与肿瘤微环境（TME）之间的关系，并结合了大量RNA和单细胞RNA数据，以分析ZNF281与免疫浸润之间的关系。体外实验验证了ZNF281敲低对细胞增殖的影响,入侵,迁移,凋亡，5-FU处理和Wnt/β-catenin通路蛋白对GC细胞DNA的损伤。
结果：ZNF281在7种癌症中高表达，并与预后相关。它是5-FU治疗的独立预后因素。ZNF281与TME评分相关，CD8T细胞丰度。ZNF281主要与DNA修复和Wnt/β-catenin途径相关。ZNF281敲低增强了5-FU对GC细胞表型的影响。
结论：我们确定并验证了ZNF281是GC中5-FU治疗的潜在影响因素之一，可能与Wnt/β-catenin通路有关。低ZNF281可能有助于改善GC患者的5-FU敏感性。
方法：我们探索了ZNF281在泛癌和正常组织中的表达差异，其表达对5-氟尿嘧啶（5-FU）治疗患者预后的影响。Cox回归分析用于确定ZNF281是否是独立的预后因素。进行富集分析以探讨ZNF281在5-FU治疗中的作用机制。我们评估了ZNF281与肿瘤微环境（TME）之间的关系，并结合了大量RNA和单细胞RNA数据，以分析ZNF281与免疫浸润之间的关系。体外实验验证了ZNF281敲低对细胞增殖的影响,入侵,迁移,凋亡，5-FU处理和Wnt/β-catenin通路蛋白对GC细胞DNA的损伤。
结果：ZNF281在7种癌症中高表达，并与预后相关。它是5-FU治疗的独立预后因素。ZNF281与TME评分相关，CD8T细胞丰度。ZNF281主要与DNA修复和Wnt/β-catenin途径相关。ZNF281敲低增强了5-FU对GC细胞表型的影响。
结论：我们确定并验证了ZNF281是GC中5-FU治疗的潜在影响因素之一，可能与Wnt/β-catenin通路有关。低ZNF281可能有助于改善GC患者的5-FU敏感性。
