Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer.
Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer.
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DOI：
10.1002/emmm.201201823
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发表时间：
2013-07
影响因子：
11.1
通讯作者：
Mori, Seiichi
中科院分区：
文献类型：
--
作者：
Tan, Tuan Zea;Miow, Qing Hao;Huang, Ruby Yun-Ju;Wong, Meng Kang;Ye, Jieru;Lau, Jieying Amelia;Wu, Meng Chu;Hadi, Luqman Hakim Bin Abdul;Soong, Richie;Choolani, Mahesh;Davidson, Ben;Nesland, Jahn M.;Wang, Ling-Zhi;Matsumura, Noriomi;Mandai, Masaki;Konishi, Ikuo;Goh, Boon-Cher;Chang, Jeffrey T.;Thiery, Jean Paul;Mori, Seiichi
上皮性卵巢癌（EOC）的特点是高度异质性。为了解决这种异质性，基于1538种肿瘤的基因表达模式开发了一种分类方案。五个生物学上不同的亚组-Epi-A、Epi-B、Mes、Stem-A和Stem-B-表现出显著不同的临床病理学特征、失调的通路和患者疾病，并使用独立的数据集进行验证。为了鉴定亚型特异性分子靶标，针对全基因组shRNA文库筛选代表这些分子亚型的卵巢癌细胞系。关注预后不良的Stem-A亚型，我们发现参与微管蛋白加工的两个基因TUBGCP4和NAT10对细胞生长至关重要，这一观察结果得到了通路分析的支持，该分析还预测了微管相关过程的参与。此外，我们观察到Stem-A细胞系确实对微管蛋白聚合抑制剂长春新碱和长春瑞滨比其他亚型更敏感。这种分型为EOC患者的新型诊断和个性化治疗的发展提供了新的见解。
Epithelial ovarian cancer (EOC) is hallmarked by a high degree of heterogeneity. To address this heterogeneity, a classification scheme was developed based on gene expression patterns of 1538 tumours. Five, biologically distinct subgroups — Epi-A, Epi-B, Mes, Stem-A and Stem-B — exhibited significantly distinct clinicopathological characteristics, deregulated pathways and patient prognoses, and were validated using independent datasets. To identify subtype-specific molecular targets, ovarian cancer cell lines representing these molecular subtypes were screened against a genome-wide shRNA library. Focusing on the poor-prognosis Stem-A subtype, we found that two genes involved in tubulin processing, TUBGCP4 and NAT10, were essential for cell growth, an observation supported by a pathway analysis that also predicted involvement of microtubule-related processes. Furthermore, we observed that Stem-A cell lines were indeed more sensitive to inhibitors of tubulin polymerization, vincristine and vinorelbine, than the other subtypes. This subtyping offers new insights into the development of novel diagnostic and personalized treatment for EOC patients.
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在412例患者的基于人群的队列中，乳腺癌的固有分子特征。
影响因子：
7.4
作者：
Calza, Stefano;Hall, Per;Auer, Gert;Bjohle, Judith;Klaar, Sigrid;Kronenwett, Ulrike;T Liu, Edison;Miller, Lance;Ploner, Alexander;Smeds, Johanna;Bergh, Jonas;Pawitan, Yudi
通讯作者：
Pawitan, Yudi
DOI：
10.1038/nrc2644
发表时间：
2009-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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DOI：
10.1073/pnas.0912708107
发表时间：
2010-04-13
影响因子：
11.1
作者：
Gatza, Michael L.;Lucas, Joseph E.;Nevins, Joseph R.
通讯作者：
Nevins, Joseph R.
影响因子：
11.2
作者：
Hendrix, ND;Wu, R;Cho, KR
通讯作者：
Cho, KR
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM