TY - JOUR
T1 - Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer
AU - Tominaga, Ei Ichiro
AU - Tsuda, Hiroshi
AU - Arao, Tokuzo
AU - Nishimura, Sadako
AU - Takano, Masashi
AU - Kataoka, Fumio
AU - Nomura, Hiroyuki
AU - Hirasawa, Akira
AU - Aoki, Daisuke
AU - Nishio, Kazuto
N1 - Funding Information:
The authors are grateful to Asami Nagata, Kanako Matsumoto, and Nozomi Tsuji for their technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture, Japan ( 20014024 ), A Grant-in Aid for scientific Research (C) from the Ministry of Education, Science and Culture, Japan ( 19591940 ), and a grant from Osaka City General Hospital .
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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=1.3-1016). 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.
AB - 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=1.3-1016). 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.
UR - http://www.scopus.com/inward/record.url?scp=77954243209&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954243209&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2010.03.010
DO - 10.1016/j.ygyno.2010.03.010
M3 - Article
C2 - 20537689
AN - SCOPUS:77954243209
SN - 0090-8258
VL - 118
SP - 160
EP - 166
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 2
ER -
