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文章:

犬骨肉瘤中FOXO4、IRF8及LEF1蛋白表达模式的免疫组织化学研究

Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma

原文发布日期:20 May 2024

DOI: 10.3390/cancers16101945

类型: Article

开放获取: 是

 

英文摘要:

Osteosarcoma (OSA) is the most common type of primary bone malignancy in people and dogs. Our previous molecular comparisons of canine OSA against healthy bone resulted in the identification of differentially expressed protein-expressing genes (forkhead box protein O4 (FOXO4), interferon regulatory factor 8 (IRF8), and lymphoid enhancer binding factor 1 (LEF1)). Immunohistochemistry (IHC) and H-scoring provided semi-quantitative assessment of nuclear and cytoplasmic staining alongside qualitative data to contextualise staining (n= 26 patients). FOXO4 was expressed predominantly in the cytoplasm with significantly lower nuclear H-scores. IRF8 H-scores ranged from 0 to 3 throughout the cohort in the nucleus and cytoplasm. LEF1 was expressed in all patients with significantly lower cytoplasmic staining compared to nuclear. No sex or anatomical location differences were observed. While reduced levels of FOXO4 might indicate malignancy, the weak or absent protein expression limits its primary use as diagnostic tumour marker. IRF8 and LEF1 have more potential for prognostic and diagnostic uses and facilitate further understanding of their roles within their respective molecular pathways, including Wnt/beta-catenin/LEF1 signalling and differential regulation of tumour suppressor genes. Deeper understanding of the mechanisms involved in OSA are essential contributions towards the development of novel diagnostic, prognostic, and treatment options in human and veterinary medicine contexts.

 

摘要翻译: 

骨肉瘤(OSA)是人类和犬类中最常见的原发性骨恶性肿瘤。我们先前对犬骨肉瘤与健康骨骼进行的分子比较,识别出差异表达的蛋白质编码基因(叉头框蛋白O4(FOXO4)、干扰素调节因子8(IRF8)和淋巴增强子结合因子1(LEF1))。通过免疫组织化学(IHC)和H评分法,我们对细胞核与细胞质染色进行了半定量评估,并结合定性数据以阐释染色背景(n=26例患者)。FOXO4主要在细胞质中表达,其细胞核H评分显著较低。IRF8在整个队列的细胞核和细胞质中H评分范围在0至3之间。LEF1在所有患者中均有表达,其细胞质染色显著低于细胞核。未观察到性别或解剖位置的差异。虽然FOXO4水平降低可能提示恶性肿瘤,但其蛋白表达微弱或缺失限制了其作为诊断性肿瘤标志物的主要用途。IRF8和LEF1在预后和诊断方面更具应用潜力,有助于进一步理解它们在各自分子通路中的作用,包括Wnt/β-连环蛋白/LEF1信号传导以及肿瘤抑制基因的差异调控。深入理解骨肉瘤的发病机制,对于在人类医学和兽医学领域开发新型诊断、预后及治疗手段具有重要贡献。

 

原文链接:

Immunohistochemical Investigation into Protein Expression Patterns of FOXO4, IRF8 and LEF1 in Canine Osteosarcoma

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