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Differential Proteomic Analysis of Nuclear Matrix in Muscle-Invasive Bladder Cancer: Potential to Improve Diagnosis and Prognosis

机译:肌肉浸润性膀胱癌中核基质的差异蛋白质组学分析:改善诊断和预后的潜力。

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Introduction: Although several molecular markers for bladder cancer have been identified, at present little information on prognostic biomarkers is available in the literature. Prognostication of this tumor is largely based on clinicopathological characteristics. Our aim was to identify nuclear matrix (NM) proteins that might serve to better characterize the phenotype of the invasive bladder cancer and to investigate their diagnostic and prognostic roles.Methods: NM proteins expressed in normal (n=3) or non-tumoral (n=9) tissue specimens and muscle-invasive bladder cancer (n=21) specimens were analyzed by two dimensional (2D) gel electrophoresis. PDQuest image analysis software was used to generate a comparative NM proteome analysis. Selected spots were characterized by liquid chromatography coupled to tandem mass spectrometry and Western blot.Results: We detected over 800 protein spots in each 2D map and 43 spots were identified. 30 proteins were differentially expressed by bladder tumor cells; among these, 19 proteins were detected in bladder tumoral tissues but not in normal and non-tumoral tissues and seven proteins correlated with tumor stage. One protein (p54nrb) was strongly correlated with vascular invasions and appeared to be also significantly (P<0.0001) associated with a decreased probability of survival.Conclusion: Important alterations in NM proteins occur in muscle-invasive bladder cancer. The differentially expressed proteins include biomarkers potentially useful for disease diagnosis, progression and prognosis. Our findings beyond improving the understanding of the biology of bladder cancer, could help to stratify patients into different prognostic subgroups and to select those who might be better candidate to multimodal therapeutic approaches.
机译:简介:尽管已鉴定出几种膀胱癌的分子标志物,但目前文献中关于预后生物标志物的信息很少。该肿瘤的预后主要基于临床病理特征。我们的目的是鉴定可能有助于更好地表征浸润性膀胱癌表型的核基质(NM)蛋白,并研究其诊断和预后作用。方法:NM蛋白以正常(n = 3)或非肿瘤( n = 9)组织标本和肌肉浸润性膀胱癌(n = 21)标本通过二维(2D)凝胶电泳进行了分析。 PDQuest图像分析软件用于生成比较NM蛋白质组分析。结果:在每个二维图谱中检测到800多个蛋白质斑点,共鉴定出43个斑点。膀胱肿瘤细胞差异表达30种蛋白质;其中,在膀胱肿瘤组织中检测到19种蛋白质,而在正常和非肿瘤组织中未检测到7种蛋白质,而与肿瘤分期相关。一种蛋白(p54nrb)与血管浸润密切相关,并且似乎也与生存率降低显着相关(P <0.0001)。结论:NM蛋白在肌肉浸润性膀胱癌中发生重要改变。差异表达的蛋白质包括可能对疾病诊断,进展和预后有用的生物标志物。我们的发现不仅可以增进对膀胱癌生物学的了解,还可以帮助将患者分为不同的预后亚组,并选择可能更适合多模式治疗方法的患者。

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