Objectives: The purpose of this study was to identify genes that predict progression-free survival (PFS) in advanced epithelial ovarian cancer (aEOC) receiving standard therapy.
Methods: We performed microarray analysis on laser microdissected aEOC cells. All cases received staging laparotomy and adjuvant chemotherapy (carboplatin+paclitaxel) as primary therapy.
Results: Microarray 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 x 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.
Conclusions: Our results suggest that GNAS gene amplification may be an independent, qualitative, and reproducible biomarker of PFS in aEOC.
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