72-Gene Classifier for Predicting Prognosis of Estrogen Receptor–Positive and Node-Negative Breast Cancer Patients Using Formalin-Fixed, Paraffin-Embedded Tumor Tissues

Nishio, Minako; Naoi, Yasuto; Tsunashima, Ryo; Nakauchi, Chiaki; Kagara, Naofumi; Shimoda, Masafumi; Shimomura, Atsushi; Maruyama, Naomi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo

doi:10.1016/j.clbc.2013.11.006

Cited by 10 publications

(6 citation statements)

References 23 publications

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“…Many studies engaged with validation of multi-gene expression classifiers in FFPE sample cohorts are confronted with compromised RT-qPCR sensitivity, shifts towards high (and variable) Cq values and high occurrence of missing data 29 . This interferes with the performance of gene-expression classifiers in FFPE material as not all genes of interest may be detected 20 30 . Therefore, implementation of gene-specific preamplification or gene-specific reverse transcription may considerably increase the success rate of validation of molecular classifiers in FFPE sample cohorts.…”

Section: Discussionmentioning

confidence: 99%

Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples

Zeka

Vanderheyden

Smet

et al. 2016

Sci Rep

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Fragmented RNA from formalin-fixed paraffin-embedded (FFPE) tissue is a known obstacle to gene expression analysis. In this study, the impact of RNA integrity, gene-specific reverse transcription and targeted cDNA preamplification was quantified in terms of reverse transcription polymerase chain reaction (RT-qPCR) sensitivity by measuring 48 protein coding genes on eight duplicate cultured cancer cell pellet FFPE samples and twenty cancer tissue FFPE samples. More intact RNA modestly increased gene detection sensitivity by 1.6 fold (earlier detection by 0.7 PCR cycles, 95% CI = 0.593–0.850). Application of gene-specific priming instead of whole transcriptome priming during reverse transcription further improved RT-qPCR sensitivity by a considerable 4.0 fold increase (earlier detection by 2.0 PCR cycles, 95% CI = 1.73–2.32). Targeted cDNA preamplification resulted in the strongest increase of RT-qPCR sensitivity and enabled earlier detection by an average of 172.4 fold (7.43 PCR cycles, 95% CI = 6.83–7.05). We conclude that gene-specific reverse transcription and targeted cDNA preamplification are adequate methods for accurate and sensitive RT-qPCR based gene expression analysis of FFPE material. The presented methods do not involve expensive or complex procedures and can be easily implemented in any routine RT-qPCR practice.

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Section: Discussionmentioning

confidence: 99%

Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples

Zeka

Vanderheyden

Smet

et al. 2016

Sci Rep

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“…With the 17-gene signature we were able to discriminate low- and high-risk patients with a high hazard ratio of 70, showing a higher discriminating value than single clinical variables (e.g., histologic grade, HR status, HER2 status). Many studies have aimed to identify gene profiles predicting response and prognosis, including commercially available panels ( van't Veer et al , 2002 ; Paik et al , 2004 ; Paik et al , 2006 ; Nishio et al , 2014 ). Most are based on node-negative early breast cancers, and include only HR− or HR+ cancers.…”

Section: Discussionmentioning

confidence: 99%

Clinical and microarray analysis of breast cancers of all subtypes from two prospective preoperative chemotherapy studies

Okuma¹,

Koizumi

Hirakawa

et al. 2016

Br J Cancer

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Background:We aimed to analyse clinical and gene expression profiles to predict pathologic complete response and disease-free survival using two consecutive, prospective, preoperative chemotherapy trial cohorts.Methods:Clinicopathological and gene expression data were evaluated in a cohort from two consecutive phase II preoperative studies that included patients with stage IIA–IIIC breast cancer of all subtypes. Analysed specimens were obtained before preoperative chemotherapy, and cDNA microarray analyses were performed using the Affymetrix Gene Chip U133 plus 2.0.Results:Between December 2005 and December 2010, 122 patients were analysed. The pathologic complete response rate was significantly higher in HER2+ and HR−/HER2− cancers. Age, pathologic complete response, HR−/HER2− status, and lymph node positivity (⩾4) were significant poor prognostic factors for disease-free survival. For the cDNA microarray analyses, sufficient tumour samples were available from 78 of the 107 patients (73%). An 8-gene signature predictive of pathologic complete response and a 17-gene signature predictive of prognosis were identified. Patients were categorised into low-risk (n=45) and high-risk groups (n=33) (HR 70.0, P=0.004).Conclusions:This study yielded preliminary data on the expression of specific genes predicting pathologic complete response and disease-free survival in a cohort of chemonaïve breast cancer patients. Further validation may distinguish those who would benefit most from perioperative chemotherapy as well as those needing further intervention.

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“…The level of ER was positively correlated with the sensitivity of the endocrine therapy and could predict tamoxifen resistance in breast cancer [ 29 ]. However, ER-positive patients are less chemosensitive than ER-negative cases [ 30 ] so that adjuvant chemotherapy might not be beneficial to some ER-positive breast tumors [ 11 ]. And ER-positive patients also have distinct behaviors and outcome due to different molecular features.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with ER-positive status which account for almost 70% of breast cancer always had a better prognosis compared with those ER-negative types [ 10 ]. However, ER-positive patients also have distinct outcomes and almost 20% might relapse within 10 years after surgery [ 11 ]. Thus, there is an urgent need to identify biomarkers that could predict prognostic outcome in patients with ER-positive breast cancer.…”

Section: Introductionmentioning

confidence: 99%

An ER-associated miRNA signature predicts prognosis in ER-positive breast cancer

Zhou

Wang

et al. 2014

J Exp Clin Cancer Res

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BackgroundBreast cancer patients with positive estrogen receptor (ER) have a better prognosis. However, no prognostic miRNA signature was reported in the ER-positive breast cancer. The aim of the study was to identify and assess the prognostic significance of a miRNA signature in ER-positive breast cancer.MethodsTwo cohorts from The Cancer Genome Atlas (TCGA) dataset were used as training (n =596) and testing set (n =319). Differential expression profiling was identified in the training set. And the prognostic value of the miRNA signature was then assessed in the two cohorts.ResultsA total of 14 miRNAs were observed to be associated with the status of ER by significance analysis of microarrays (SAM) in the training set. Patients were characterized as high score or low score group according to the calculated risk scores from each miRNA. And patients in high score group had worse overall survival compared with those in low score group both in the training and testing set.ConclusionsOur study revealed a miRNA signature including 14 miRNAs associated with ER status which could act as a prognostic marker in ER-positive breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-014-0094-5) contains supplementary material, which is available to authorized users.

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72-Gene Classifier for Predicting Prognosis of Estrogen Receptor–Positive and Node-Negative Breast Cancer Patients Using Formalin-Fixed, Paraffin-Embedded Tumor Tissues

Cited by 10 publications

References 23 publications

Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples

Straightforward and sensitive RT-qPCR based gene expression analysis of FFPE samples

Clinical and microarray analysis of breast cancers of all subtypes from two prospective preoperative chemotherapy studies

An ER-associated miRNA signature predicts prognosis in ER-positive breast cancer

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