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ASPM 和微管相关蛋白在卵巢上皮性癌中的表达与肿瘤分级和生存相关。

ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival.

机构信息

Section of Ophthalmology and Neurosciences, Leeds Institute of Molecular Medicine, Welcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, UK.

出版信息

Br J Cancer. 2011 May 10;104(10):1602-10. doi: 10.1038/bjc.2011.117. Epub 2011 Apr 19.

Abstract

BACKGROUND

The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephaly-associated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers.

METHODS

Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data.

RESULTS

A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival.

CONCLUSION

Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cancer.

摘要

背景

上皮性卵巢癌(EOC)的临床病理和分子异质性使其早期诊断和成功治疗变得复杂。高度非整倍体肿瘤和腹水的存在是 EOC 的标志。两个小头畸形相关蛋白,异常纺锤体小头畸形相关蛋白(ASPM)和微管蛋白,参与有丝分裂和 DNA 损伤修复。它们的表达在 EOC 的 RNA 水平上受到调节。在这里,通过蛋白斑点印迹和/或免疫荧光确定从小鼠腹水建立的原发性培养物中 ASPM 和微管蛋白的表达,并与临床数据相关联,以评估它们作为生物标志物的适用性。

方法

通过蛋白斑点印迹和/或免疫荧光分析五个已建立的卵巢癌细胞系、两个良性卵巢腹水样本的细胞和 40 个从小鼠腹水样本中建立的 EOC 原发性培养物,以确定 ASPM 和微管蛋白蛋白水平及其细胞定位。结果与临床病理数据相关联。

结果

ASPM 定位与肿瘤分级之间存在统计学显著相关性,高水平的细胞质 ASPM 与 1 级肿瘤相关。相反,细胞质微管蛋白仅在高级别肿瘤中被鉴定。此外,核微管蛋白水平低与患者生存时间缩短相关。

结论

我们的结果表明,ASPM 和微管蛋白有可能成为卵巢癌的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3feb/3101901/def44a9395b6/bjc2011117f1.jpg

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