Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer.
Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer.
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DOI：
10.1016/j.ygyno.2010.03.010
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发表时间：
2010-08
影响因子：
4.7
通讯作者：
E. Tominaga;H. Tsuda;T. Arao;S. Nishimura;M. Takano;F. Kataoka;H. Nomura;A. Hirasawa;D. Aoki;K. Nishio
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文献类型：
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作者：
E. Tominaga;H. Tsuda;T. Arao;S. Nishimura;M. Takano;F. Kataoka;H. Nomura;A. Hirasawa;D. Aoki;K. Nishio
本研究的目的是确定基因预测无进展生存（PFS）在晚期上皮性卵巢癌（aEOC）接受标准therapy. METHODS我们进行了微阵列分析激光显微切割aEOC细胞。所有病例均接受分期剖腹手术和辅助化疗（卡铂+紫杉醇）作为主要治疗。RT-PCR微阵列分析确定了50个基因在无疾病证据（N艾德）和有疾病证据（艾德）患者肿瘤中的差异表达（p<0.001）。其中6个基因（13%）位于8 q24，9个基因（19.6%）位于20 q11 -13。8号和20号染色体中的选择基因集/分析基因集的比率显著高于其他染色体区域（6/606 vs. 32/13656，p=0.01）和（12/383 vs. 32/13656，p=1.3×10−16）。我们推测异常的染色体分布是由于基因组改变，这些基因可能在aEOC中起重要作用，并根据p值和倍数变化选择20 q13上的GNAS（GNAS复合基因座，NM_000516）。aEOC细胞的基因组PCR也显示GNAS的扩增与不利的PFS显著相关（p=0.011）。对独立样本的实时定量RT-PCR分析显示，位于染色体20 q13的GNAS基因的高mRNA表达水平是无进展生存期（PFS）的显著不利指标。最后，GNAS扩增是一个独立的预后因素PFS.CONCLUSIONSOUR的结果表明，GNAS基因扩增可能是一个独立的，定性的，和可重复的生物标志物PFS在aEOC。
OBJECTIVESThe purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy.METHODSWe performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin+paclitaxel) as primary therapy.RESULTSMicroarray analysis identified 50 genes differentially expressed between tumors of patients with no evidence of disease (NED) or evidence of disease (ED) (p<0.001). Six genes (13%) were located at 8q24, and 9 genes (19.6%), at 20q11–13. The ratio of selected gene set/analyzed gene set in chromosomes 8 and 20 are significantly higher than that in other chromosome regions (6/606 vs. 32/13656, p=0.01) and (12/383 vs. 32/13656, p=1.3×10−16). We speculate that the abnormal chromosomal distribution is due to genomic alteration and that these genes may play an important role in aEOC and choose GNAS (GNAS complex locus, NM_000516) on 20q13 based on the p value and fold change. Genomic PCR of aEOC cells also showed that amplification of GNAS was significantly correlated with unfavorable PFS (p=0.011). Real-time quantitative RT-PCR analysis of independent samples revealed that high mRNA expression levels of the GNAS genes, located at chromosome 20q13, was significantly unfavorable indicators of progression-free survival (PFS). Finally, GNAS amplification was an independent prognostic factor for PFS.CONCLUSIONSOur results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC.