Angiogenic mRNA and microRNA gene expression signature predicts a novel subtype of serous ovarian cancer.
Angiogenic mRNA and microRNA gene expression signature predicts a novel subtype of serous ovarian cancer.
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DOI：
10.1371/journal.pone.0030269
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Matulonis UA
中科院分区：
文献类型：
--
作者：
Bentink S;Haibe-Kains B;Risch T;Fan JB;Hirsch MS;Holton K;Rubio R;April C;Chen J;Wickham-Garcia E;Liu J;Culhane A;Drapkin R;Quackenbush J;Matulonis UA
卵巢癌是美国女性癌症死亡的第五大原因，也是全球第七大致死原因。尽管卵巢癌以其最初对铂类药物的敏感性而闻名，但绝大多数患者最终会发展为复发性癌症，并死于越来越多的铂耐药疾病。现代靶向癌症药物干预细胞信号，识别关键的疾病机制和途径将极大地提高我们的治疗能力。为了阐明卵巢癌的分子多样性，我们对129例晚期、高级别浆液性卵巢癌进行了全面的转录图谱分析。我们实现了一个基于重新采样的ISIS类发现算法(RISIS：Robust ISIS)的版本，并将其应用于整个卵巢癌转录图谱集。RISS发现了一种以前未描述的患者分层，进一步得到了microRNA表达谱的支持，基因集浓缩分析发现细胞外基质、细胞黏附和血管生成基因对分层提供了强大的生物学支持。相应的“血管生成特征”在10个已发表的独立卵巢癌基因表达数据集中得到验证，并与总存活率显著相关。我们定义的亚型具有潜在的翻译兴趣，因为它们可能与识别可能受益于目前正在临床试验中的抗血管生成治疗的患者相关。
Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the seventh most fatal worldwide. Although ovarian cancer is notable for its initial sensitivity to platinum-based therapies, the vast majority of patients eventually develop recurrent cancer and succumb to increasingly platinum-resistant disease. Modern, targeted cancer drugs intervene in cell signaling, and identifying key disease mechanisms and pathways would greatly advance our treatment abilities. In order to shed light on the molecular diversity of ovarian cancer, we performed comprehensive transcriptional profiling on 129 advanced stage, high grade serous ovarian cancers. We implemented a, re-sampling based version of the ISIS class discovery algorithm (rISIS: robust ISIS) and applied it to the entire set of ovarian cancer transcriptional profiles. rISIS identified a previously undescribed patient stratification, further supported by micro-RNA expression profiles, and gene set enrichment analysis found strong biological support for the stratification by extracellular matrix, cell adhesion, and angiogenesis genes. The corresponding “angiogenesis signature” was validated in ten published independent ovarian cancer gene expression datasets and is significantly associated with overall survival. The subtypes we have defined are of potential translational interest as they may be relevant for identifying patients who may benefit from the addition of anti-angiogenic therapies that are now being tested in clinical trials.
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影响因子：
14.9
作者：
Chen, Jing;Lozach, Jean;Wickham, Eliza;Barnes, Garcia Bret;Luo, Shujun;Mikoulitch, Ivan;Zhou, Lixin;Schroth, Gary;Fan, Jian-Bing
通讯作者：
Fan, Jian-Bing
影响因子：
45.3
作者：
Matulonis, Ursula A.;Berlin, Suzanne;Penson, Richard T.
通讯作者：
Penson, Richard T.
影响因子：
4.4
作者：
Kapp, Amy V.;Jeffrey, Stefanie S.;Langerod, Anita;Borresen-Dale, Anne-Lise;Han, Wonshik;Noh, Dong-Young;Bukholm, Ida R. K.;Nicolau, Monica;Brown, Patrick O.;Tibshirani, Robert
通讯作者：
Tibshirani, Robert
影响因子：
4.7
作者：
Liu, Joyce F.;Hirsch, Michelle S.;Matulonis, Ursula A.
通讯作者：
Matulonis, Ursula A.
影响因子：
45.3
作者：
Burger, Robert A.;Sill, Michael W.;Sorosky, Joel I.
通讯作者：
Sorosky, Joel I.