Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression.
Deregulation of microcephalin and ASPM expression are correlated with epithelial ovarian cancer progression.
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DOI：
10.1371/journal.pone.0097059
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bell SM
中科院分区：
文献类型：
--
作者：
Alsiary R;Brüning-Richardson A;Bond J;Morrison EE;Wilkinson N;Bell SM
MCPH1（小头蛋白）和 ASPM（异常纺锤样小头畸形相关）基因突变会导致原发性小头畸形。两者都是参与有丝分裂的中心体相关蛋白。小头磷脂在 DNA 损伤反应中发挥着重要作用，ASPM 是发育中大脑的增殖性神经上皮细胞正确分裂所必需的。 MCPH1 mRNA 表达减少和 ASPM mRNA 过度表达与人类癌症的发展有关。上皮性卵巢癌（EOC）的特点是高度非整倍体肿瘤。之前我们报道过低小头磷脂和高 ASPM 蛋白水平以及与腹水恶性细胞的临床病理参数的关联。为了在更大规模上证实这些先前的发现，通过免疫组织化学在两个队列中评估了小头磷脂和 ASPM 的表达水平和定位； 25 个样本的训练集和 322 个 EOC 组织样本的验证集。结果与相关的组织病理学数据相关。在正常卵巢组织中，小头磷脂核染色模式始终很强。在癌症组织中，我们在高级别和晚期肿瘤中发现了低核小头磷脂表达（分别为 p<0.0001 和 p = 0.0438）。 ASPM 在正常组织中具有中度至高度的核表达和低度至中度的细胞质表达。在 EOC 浆液性亚型中，细胞质 ASPM 表达随着肿瘤分级和分期而降低（分别为 p = 0.023 和 p = 0.011）。在子宫内膜样亚型中，细胞质 ASPM 随着肿瘤分期而增加 (p = 0.023)。肿瘤侵袭性 (T3) 和淋巴结受累 (N1) 的增加也与 EOC 中细胞质 ASPM 的减少相关（分别为 p = 0.02 和 p = 0.04）。我们通过在更大规模的肿瘤组织研究中确认低核小头磷脂水平和高细胞质 ASPM 水平之间的关联，验证了之前关于 EOC 中小头磷脂和 ASPM 表达失调的发现。小头磷脂和 ASPM 可能被证明是 EOC 中有用的生物标志物。
Mutations in the MCPH1 (Microcephalin) and ASPM (abnormal spindle-like microcephaly associated) genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developing brain. Reduced MCPH1 mRNA expression and ASPM mRNA over-expression have been implicated in the development of human carcinomas. Epithelial ovarian cancer (EOC) is characterised by highly aneuploid tumours. Previously we have reported low Microcephalin and high ASPM protein levels and associations with clinico-pathological parameters in malignant cells from ascitic fluids. To confirm these previous findings on a larger scale Microcephalin and ASPM expression levels and localisations were evaluated by immunohistochemistry in two cohorts; a training set of 25 samples and a validation set of 322 EOC tissue samples. Results were correlated to the associated histopathological data. In normal ovarian tissues the Microcephalin nuclear staining pattern was consistently strong. In the cancer tissues, we identified low nuclear Microcephalin expression in high grade and advanced stage tumours (p<0.0001 and p = 0.0438 respectively). ASPM had moderate to high nuclear and low to moderate cytoplasmic expression in normal tissue. Cytoplasmic ASPM expression decreased with tumour grade and stage in the serous subtype of EOC (p = 0.023 and p = 0.011 respectively). Cytoplasmic ASPM increased with tumour stage in the endometrioid subtype (p = 0.023). Increasing tumour invasiveness (T3) and lymph node involvement (N1) also correlated with a decrease in cytoplasmic ASPM in EOC (p = 0.02 and p = 0.04 respectively). We have validated previous findings of deregulated expression of Microcephalin and ASPM in EOC by confirming associations for low nuclear Microcephalin levels and high cytoplasmic ASPM levels in a larger scale tumour tissue study. Microcephalin and ASPM may prove useful biomarkers in EOC.
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影响因子：
3.7
作者：
Drozdov I;Bornschein J;Wex T;Valeyev NV;Tsoka S;Malfertheiner P
通讯作者：
Malfertheiner P
影响因子：
9.8
作者：
Guernsey, Duane L.;Jiang, Haiyan;Samuels, Mark E.
通讯作者：
Samuels, Mark E.
影响因子：
5.8
作者：
Bikeye SN;Colin C;Marie Y;Vampouille R;Ravassard P;Rousseau A;Boisselier B;Idbaih A;Calvo CF;Leuraud P;Lassalle M;El Hallani S;Delattre JY;Sanson M
通讯作者：
Sanson M
DOI：
10.1093/jnci/85.3.200
发表时间：
1993-02-03
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
ALLRED, DC;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
4.2
作者：
Hagemann, Carsten;Anacker, Jelena;Vince, Giles Hamilton
通讯作者：
Vince, Giles Hamilton