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Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets.

Yoshihara K, Tajima A, Yahata T, Kodama S, Fujiwara H, Suzuki M, Onishi Y, Hatae M, Sueyoshi K, Fujiwara H, Kudo Y, Kotera K, Masuzaki H, Tashiro H, Katabuchi H, Inoue I, Tanaka K - PLoS ONE (2010)

Bottom Line: However, there is a wide range of outcomes for individual patients.In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008).Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

ABSTRACT

Background: Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer.

Methodology/principal findings: Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66-5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).

Conclusions/significance: The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.

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Related in: MedlinePlus

Validation of microarray expression data using quantitative real-time reverse transcript polymerase chain reaction (RT-PCR) analysis.There were significant correlations between microarray expression and real-time RT-PCR expression in (A) E2F2, (B) DNAH7, (C) FOXJ1, and (D) FILIP1.
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pone-0009615-g002: Validation of microarray expression data using quantitative real-time reverse transcript polymerase chain reaction (RT-PCR) analysis.There were significant correlations between microarray expression and real-time RT-PCR expression in (A) E2F2, (B) DNAH7, (C) FOXJ1, and (D) FILIP1.

Mentions: To validate the microarray expression data, we performed quantitative real-time RT-PCR for a subset of the discovery dataset (53 samples). The four genes, E2F2, FOXJ1, DNAH7, and FILIP1, were randomly selected for this purpose. There were significant correlations between microarray expression data and real-time RT-PCR expression data (Figure 2). In spite of the smaller sample size, we confirmed a significant association between PFS time and each of the real-time RT-PCR data for the four genes in the univariate Cox hazard model (data not shown).


Gene expression profile for predicting survival in advanced-stage serous ovarian cancer across two independent datasets.

Yoshihara K, Tajima A, Yahata T, Kodama S, Fujiwara H, Suzuki M, Onishi Y, Hatae M, Sueyoshi K, Fujiwara H, Kudo Y, Kotera K, Masuzaki H, Tashiro H, Katabuchi H, Inoue I, Tanaka K - PLoS ONE (2010)

Validation of microarray expression data using quantitative real-time reverse transcript polymerase chain reaction (RT-PCR) analysis.There were significant correlations between microarray expression and real-time RT-PCR expression in (A) E2F2, (B) DNAH7, (C) FOXJ1, and (D) FILIP1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2837379&req=5

pone-0009615-g002: Validation of microarray expression data using quantitative real-time reverse transcript polymerase chain reaction (RT-PCR) analysis.There were significant correlations between microarray expression and real-time RT-PCR expression in (A) E2F2, (B) DNAH7, (C) FOXJ1, and (D) FILIP1.
Mentions: To validate the microarray expression data, we performed quantitative real-time RT-PCR for a subset of the discovery dataset (53 samples). The four genes, E2F2, FOXJ1, DNAH7, and FILIP1, were randomly selected for this purpose. There were significant correlations between microarray expression data and real-time RT-PCR expression data (Figure 2). In spite of the smaller sample size, we confirmed a significant association between PFS time and each of the real-time RT-PCR data for the four genes in the univariate Cox hazard model (data not shown).

Bottom Line: However, there is a wide range of outcomes for individual patients.In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008).Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

ABSTRACT

Background: Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer.

Methodology/principal findings: Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66-5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20-1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008).

Conclusions/significance: The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.

Show MeSH
Related in: MedlinePlus