Overexpression of chromatin assembly factor-1 p60, poly(ADP-ribose) polymerase 1 and nestin predicts metastasizing behaviour of oral cancer.

Overexpression of chromatin assembly factor-1 p60, poly(ADP-ribose) polymerase 1 and nestin predicts metastasizing behaviour of oral cancer.
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DOI:
10.1111/j.1365-2559.2012.04313.x
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发表时间:
2012-12
期刊:
影响因子:
6.4
通讯作者:
Staibano S
Staibano S
中科院分区:
医学2区
文献类型:
--
作者:
Mascolo M;Ilardi G;Romano MF;Celetti A;Siano M;Romano S;Luise C;Merolla F;Rocco A;Vecchione ML;De Rosa G;Staibano S

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口腔鳞状细胞癌(OSCC)的自然病程是可变的,难以预测。本研究旨在评估PARP-1、CAF-1/p60和干细胞标志物CD 133、CD 166、CD 44、CD 44 v6和巢蛋白作为OSCC患者预后和无进展生存期标志物的价值。收集了66例(41例男性和25例女性,年龄29-92岁)接受手术治疗舌、底、唇和腭OSCC的临床数据。在随访期间(范围:12-131个月),14例患者发生复发/转移和/或死亡。通过石蜡包埋的肿瘤组织的免疫组织化学、肿瘤蛋白裂解物和人细胞系的蛋白质印迹分析以及RNA沉默测定来进行该研究。此外,原发性肿瘤的人乳头瘤病毒(HPV)状态通过免疫组织化学和病毒亚型进行了评价。进行单变量和多变量分析,以确定这些参数与研究人群的临床和病理变量之间的相关性。我们发现PARP-1high/CAF-1 p60 high/nestinhigh表型表征了预后最差的OSCC(所有HPV阴性)。这在临床治疗中可能是有益的,因为放射性增强抗PARP-1和/或抗CAF-1/p60药物可能允许在巢蛋白过表达、转移性OSCC细胞中绕过放射抗性。
The natural history of oral squamous cell carcinomas (OSCCs) is variable and difficult to predict. This study aimed to assess the value of the expression of poly(ADP-ribose) polymerase 1 (PARP-1), chromatin assembly factor-1 (CAF-1)/p60 and the stem cell markers CD133, CD166, CD44, CD44v6 and nestin as markers of outcome and progression-free survival in OSCC patients. Clinical data were collected from 66 patients (41 male and 25 female, aged 29–92 years) who underwent surgery for OSCC of the tongue, floor, lips, and palate. During follow-up (range: 12–131 months), 14 patients experienced relapse/metastasis and/or death. The study was performed by immunohistochemistry on paraffin-embedded tumour tissues, western blot analysis of tumour protein lysates and human cell lines, and RNA silencing assays. In addition, the human papillomavirus (HPV) status of primary tumours was evaluated by immunohistochemistry and viral subtyping. Univariate and multivariate analyses were performed to determine the correlation between these parameters and the clinical and pathological variables of the study population. We found that a PARP-1high/CAF-1 p60high/nestinhigh phenotype characterized the OSCCs with the worst prognosis (all HPV-negative). This may be of benefit in clinical management, since radio-enhancing anti-PARP-1 and/or anti-CAF-1/p60 agents may allow radioresistance to be bypassed in the nestin-overexpressing, metastasizing OSCC cells.
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