Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer

Ei Ichiro Tominaga, Hiroshi Tsuda, Tokuzo Arao, Sadako Nishimura, Masashi Takano, Fumio Kataoka, Hiroyuki Nomura, Akira Hirasawa, Daisuke Aoki, Kazuto Nishio

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)160-166
Number of pages7
JournalGynecologic Oncology
Volume118
Issue number2
DOIs
Publication statusPublished - Aug 1 2010
Externally publishedYes

Fingerprint

Disease-Free Survival
Biomarkers
Genes
Microarray Analysis
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 6
Ovarian epithelial cancer
Gene Amplification
Carboplatin
Adjuvant Chemotherapy
Paclitaxel
Laparotomy
Real-Time Polymerase Chain Reaction
Lasers
Chromosomes
Polymerase Chain Reaction
Messenger RNA
Therapeutics
Neoplasms

Keywords

  • Amplification
  • Biomarker
  • Carboplatin
  • Ovarian cancer
  • Paclitexal
  • Prognosis

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer. / Tominaga, Ei Ichiro; Tsuda, Hiroshi; Arao, Tokuzo; Nishimura, Sadako; Takano, Masashi; Kataoka, Fumio; Nomura, Hiroyuki; Hirasawa, Akira; Aoki, Daisuke; Nishio, Kazuto.

In: Gynecologic Oncology, Vol. 118, No. 2, 01.08.2010, p. 160-166.

Research output: Contribution to journalArticle

Tominaga, Ei Ichiro ; Tsuda, Hiroshi ; Arao, Tokuzo ; Nishimura, Sadako ; Takano, Masashi ; Kataoka, Fumio ; Nomura, Hiroyuki ; Hirasawa, Akira ; Aoki, Daisuke ; Nishio, Kazuto. / Amplification of GNAS may be an independent, qualitative, and reproducible biomarker to predict progression-free survival in epithelial ovarian cancer. In: Gynecologic Oncology. 2010 ; Vol. 118, No. 2. pp. 160-166.
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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

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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.

KW - Amplification

KW - Biomarker

KW - Carboplatin

KW - Ovarian cancer

KW - Paclitexal

KW - Prognosis

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