2012年4月9日,，來自杜克大學(xué)醫(yī)學(xué)中心的科學(xué)家已經(jīng)確定基因“開/關(guān)”分子，用來定義臨床卵巢癌相關(guān)的分子亞型,，指出了臨床預(yù)后和診斷測試中理想的潛在治療靶標(biāo)。這些雙峰基因可以定義有不同預(yù)后情況的腫瘤亞型,，便于實(shí)施不同的治療方案,。研究人員的研究結(jié)果發(fā)表在《分子診斷雜志》上。
首席研究員Michael B. Datto博士解釋說：我們確定了一套很小的基因,，這些基因有可能成為強(qiáng)大的上皮性卵巢癌的預(yù)后指標(biāo),。
卵巢癌在婦科惡性腫瘤中死亡率最高，是第五個(gè)最常見的婦女癌癥死亡的原因,。漿液性癌（卵巢上皮性惡性腫瘤中最常見的類型）的預(yù)后方法仍然相對不準(zhǔn)確,。目前晚期腫瘤患者多數(shù)預(yù)后較差。然而,，在這一群體有對持久的化療有反應(yīng)的患者群體,，有更好的生存期。
基于乳腺癌的早期研究工作,，Datto博士和他的同事們推測卵巢上皮癌中存在臨床相關(guān)的雙峰基因。他們使用一個(gè)大的,、公開的卵巢癌微陣列數(shù)據(jù)集,，采用一種算法評估285樣本中所有的基因表達(dá)情況。他們鑒定出許多基因具有強(qiáng)大的雙峰表達(dá)模式,。他們還發(fā)現(xiàn)雙峰表達(dá)模式的基因數(shù)量與腫瘤的類型和/或整體病人的生存情況顯著相關(guān),。
Datto博士表示從臨床試驗(yàn)的角度來看，基因連續(xù)表達(dá)模式使得測試變得困難,。然而,，一個(gè)特定的雙峰基因“關(guān)/閉”的表達(dá)的區(qū)別是相對簡單的。同時(shí)研究人員表示雙峰基因也可能是免疫組化定量等測試方法潛在的候選指標(biāo),。
研究人員發(fā)現(xiàn)已知的幾個(gè)雙峰基因在腫瘤形成中的作用,。博士Datto總結(jié)道：我們所描述的分子開關(guān)基因?qū)⒉粌H是在卵巢癌中，也許在多個(gè)腫瘤類型也有作用,。（生物谷：Bioon）
doi:10.1016/j.jmoldx.2012.01.007
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PMID:
Genes with Bimodal Expression Are Robust Diagnostic Targets that Define Distinct Subtypes of Epithelial Ovarian Cancer with Different Overall Survival
Dawn N. Kernagis, Allison H.S. Hall, Michael B. Datto
In some cancer types, certain genes behave as molecular switches, with on and off expression states. These genes tend to define tumor subtypes associated with different treatments and different patient survival. We hypothesized that clinically relevant molecular switch genes exist in epithelial ovarian cancer. To test this hypothesis, we applied a bimodal discovery algorithm to a publicly available ovarian cancer expression microarray data set, GSE9891 [285 tumors: 246 malignant serous (MS), 20 endometrioid (EM), and 18 low malignant potential (LMP) ovarian carcinomas]. Genes with robust bimodal expression patterns were identified across all ovarian tumor types and also within selected subtypes: 73 bimodal genes demonstrated differential expression between LMP versus MS and EM; 22 bimodal genes distinguished MS from EM; and 14 genes had significant association with survival among MS tumors. When these genes were combined into a single survival score, the median survival for patients with a favorable versus unfavorable score was 65 versus 29 months (P < 0.0001, hazard ratio = 0.4221). Two independent data sets [high-grade, advanced-stage serous (n = 53) and advanced-stage (n = 119) ovarian tumors] validated the survival score performance. We conclude that genes with bimodal expression patterns not only define clinically relevant molecular subtypes of ovarian carcinoma but also provide ideal targets for translation into the clinical laboratory.
