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Aurora B Expression as a Prognostic Indicator and Possibile Therapeutic Target in Oral Squamous Cell Carcinoma

机译:Aurora B表达作为口腔鳞状细胞癌的预后指标和可能的治疗靶标

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The aim of this study is to investigate the expression of the chromosomal passenger protein Aurora B and its activated (phosphorylated) form in a large series of human oral squamous cell cancers (OSCC) and to evaluate its clinical and prognostic significance. Western blotting analysis revealed overexpression of both Aurora B and Thr-232 Phopsho-Aurora B in OSCC lines as compared to normal keratinocytes and bladder cancer cells. Furthermore, protein expression was analysed by immunohistochemistry in 101 OSCC of different site, stage and histological grade and in normal peritumoural areas. The intracellular localization of Aurora B in tumour cells was mainly nuclear, especially in proliferative areas, and significant overexpression was found in tumours in comparison to normal peritumoural areas (P=0.012). Staining results were correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and tumour stage (stage II, III and IV vs stage I, P=0.030) and size (2cm, P=0.010). Cox regression analysis confirmed a poorer disease-free survival in cases with high expression of Aurora B protein. Kaplan-Meier curves showed shorter time to progression in patients with high levels of Aurora B expression (p<0.05). Moreover, the tumoral group with nuclear Aurora B immunolocalization had the worst prognosis (P=0.0364 in disease free survival). Our results suggest that assessing Aurora B expression might help in patients' risk stratification and serve as a novel therapeutic target in advanced OSCCs.
机译:这项研究的目的是研究染色体客源蛋白Aurora B及其活化(磷酸化)形式在一系列人类口腔鳞状细胞癌(OSCC)中的表达,并评估其临床和预后意义。 Western印迹分析表明,与正常角质形成细胞和膀胱癌细胞相比,Aurora B和Thr-232 Phopsho-Aurora B在OSCC系中均过表达。此外,通过免疫组织化学分析了在不同部位,阶段和组织学等级的101 OSCC以及正常肿瘤周围区域中的蛋白质表达。 Aurora B在肿瘤细胞中的细胞内定位主要是核内的,尤其是在增生区域,与正常肿瘤周围区域相比,在肿瘤中发现了明显的过表达(P = 0.012)。染色结果与临床病理参数和长期随访相关,发现蛋白质表达与肿瘤分期(II,III和IV期与I期,P = 0.030)和大小(2cm,P = 0.010)之间存在显着相关)。 Cox回归分析证实了在Aurora B蛋白高表达的情况下无病生存期较差。 Kaplan-Meier曲线显示高水平Aurora B表达患者的病程进展时间较短(p <0.05)。此外,具有核Aurora B免疫定位的肿瘤组的预后最差(无病生存期P = 0.0364)。我们的结果表明,评估Aurora B的表达可能有助于患者的风险分层,并且可以作为晚期OSCC中的新型治疗靶点。

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