ZNF385B and VEGFA Are Strongly Differentially Expressed in Serous Ovarian Carcinomas and Correlate with Survival
ZNF385B and VEGFA Are Strongly Differentially Expressed in Serous Ovarian Carcinomas and Correlate with Survival
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DOI：
10.1371/journal.pone.0046317
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发表时间：
2012-09-28
期刊：
影响因子：
3.7
通讯作者：
Gautvik, Kaare M.
中科院分区：
文献类型：
--
作者：
Elgaaen, Bente Vilming;Olstad, Ole Kristoffer;Gautvik, Kaare M.
背景：卵巢癌的发生机制尚不清楚。本研究的目的是鉴定中等分化和低分化（MD/PD）浆液性卵巢癌（SC）、浆液性卵巢交界性肿瘤（SBOT）和正常卵巢浅表刮片（SNO）之间差异表达的mRNA，并将这些mRNA与包括生存率在内的临床参数相关联。通过全局基因表达谱分析MD/PD SC、SBOT和SNO之间mRNA表达的差异（n = 23），结果：筛选出30条MD/PD SC、SBOT和SNO间差异表达的mRNA，其中21条经RT-qPCR验证（p < 0.01）。其中，13种mRNA在MD/PD SC中与SNO相比差异表达（p，0.01），并且与临床参数相关。ZNF 385 B表达下调（FC =-130.5，p = 1.2 × 10 - 7），与总生存期相关（p = 0.03）。VEGFA上调（FC = 6.1，p = 6.0 x 10（-6）），与无进展生存期相关（p = 0.037）。TPX 2和FOXM 1 mRNA水平升高（分别为FC = 28.5，p = 2.7 x 10（-10）和FC = 46.2，p = 5.6 x 10（-4））与CA 125正常化相关（分别为p = 0.03和p = 0.044）。此外，我们还提出了MD/PD SC的分子通路，包括VEGFA、FOXM 1、TPX 2、BIRC 5和TOP 2A，它们都显著上调并与TP 53直接相互作用。
Background: The oncogenesis of ovarian cancer is poorly understood. The aim of this study was to identify mRNAs differentially expressed between moderately and poorly differentiated (MD/PD) serous ovarian carcinomas (SC), serous ovarian borderline tumours (SBOT) and superficial scrapings from normal ovaries (SNO), and to correlate these mRNAs with clinical parameters including survival.Methods: Differences in mRNA expression between MD/PD SC, SBOT and SNO were analyzed by global gene expression profiling (n = 23), validated by RT-qPCR (n = 41) and correlated with clinical parameters.Results: Thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected from the global gene expression analyses, and 21 were verified (p < 0.01) by RT-qPCR. Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p, 0.01) and were correlated with clinical parameters. ZNF385B was downregulated (FC = -130.5, p = 1.2 x 10(-7)) and correlated with overall survival (p = 0.03). VEGFA was upregulated (FC = 6.1, p = 6.0 x 10(-6)) and correlated with progression-free survival (p = 0.037). Increased levels of TPX2 and FOXM1 mRNAs (FC = 28.5, p = 2.7 x 10(-10) and FC = 46.2, p = 5.6 x 10(-4), respectively) correlated with normalization of CA125 (p = 0.03 and p = 0.044, respectively). Furthermore, we present a molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and directly interacting with TP53.Conclusions: We have identified 21 mRNAs differentially expressed (p