Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA185677 | ENA |
REPOSITORIES: ENA
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Project description:Genomic Grade Index (GGI) is a 97-gene signature that improves histologic grade (HG) classification in invasive breast carcinoma. In this prospective study we sought to evaluate the feasibility of performing GGI in routine clinical practice and its impact on treatment recommendations. Patients with pT1pT2 or operable pT3, N0-3 invasive breast carcinoma were recruited from 8 centers in Belgium. Fresh surgical samples were sent at room temperature in the MapQuant DxM-bM-^DM-" PathKit for centralized genomic analysis. Genomic profiles were determined using Affymetrix U133 Plus 2.0 and GGI calculated using the MapQuant DxM-bM-^DM-" protocol, which defines tumors as low or high Genomic Grade (GG-1 and GG-3 respectively). 180 pts were recruited and 155 were eligible. The MapQuant test was performed in 142 cases and GGI was obtained in 78% of cases (n=111). Reasons for failures were 15 samples with <30% of invasive tumor cells (11%), 15 with insufficient RNA quality (10%), and 1 failed hybridization (<1%). For tumors with an available representative sample (M-bM-^IM-% 30% inv. tumor cells) (n=127), the success rate was 87.5 %. GGI reclassified 69% of the 54 HG2 tumors as GG-1 (54%) or GG-3 (46%). Changes in treatment recommendations occurred mainly in the subset of HG2 tumors reclassified into GG-3, with increased use of chemotherapy in this subset. The use of GGI is feasible in routine clinical practice and impacts treatment decisions in early-stage breast cancer. Total RNA was extracted from fresh tumor tissues comprising M-bM-^IM-%30% invasive tumor cells and hybridized on Affymetrix microarrays if the RIN was M-bM-^IM-% 7.
2013-06-03 | E-GEOD-43365 | biostudies-arrayexpress
Project description:Genomic Grade Index (GGI) is a 97-gene signature that improves histologic grade (HG) classification in invasive breast carcinoma. In this prospective study we sought to evaluate the feasibility of performing GGI in routine clinical practice and its impact on treatment recommendations. Patients with pT1pT2 or operable pT3, N0-3 invasive breast carcinoma were recruited from 8 centers in Belgium. Fresh surgical samples were sent at room temperature in the MapQuant Dx™ PathKit for centralized genomic analysis. Genomic profiles were determined using Affymetrix U133 Plus 2.0 and GGI calculated using the MapQuant Dx™ protocol, which defines tumors as low or high Genomic Grade (GG-1 and GG-3 respectively). 180 pts were recruited and 155 were eligible. The MapQuant test was performed in 142 cases and GGI was obtained in 78% of cases (n=111). Reasons for failures were 15 samples with <30% of invasive tumor cells (11%), 15 with insufficient RNA quality (10%), and 1 failed hybridization (<1%). For tumors with an available representative sample (≥ 30% inv. tumor cells) (n=127), the success rate was 87.5 %. GGI reclassified 69% of the 54 HG2 tumors as GG-1 (54%) or GG-3 (46%). Changes in treatment recommendations occurred mainly in the subset of HG2 tumors reclassified into GG-3, with increased use of chemotherapy in this subset. The use of GGI is feasible in routine clinical practice and impacts treatment decisions in early-stage breast cancer.
2013-06-03 | GSE43365 | GEO
Project description:Based on fuzzy logic selection and classification algorithms, our selection method measures the contribution of each gene for each of two pre-defined classes in order to find the best discrimination. This algorithm extracts and ranks the most pertinent markers, since it is based on feature weighting according to optimal error rate, sensitivity and specificity. We applied the fuzzy logic selection on four breast cancer microarray databases to obtain new gene signatures based on histological grade. To validate these gene signatures, we designed probes for the selected genes on Nimblegen custom microarrays and tested them on a series of 151 consecutive invasive breast carcinomas displaying clinicopathological features similar to those observed in routine practice. 151 frozen breast cancer tumors from the tumor bank of the Claudius Regaud Institute (ICR Toulouse, France) were selected. This cohort consisted of consecutive invasive breast carcinoma patients treated at Claudius Regaud Institute between 2009 and 2011. All patients included in this cohort signed an informed consent. Clinico-pathological characteristics of the series were similar to those observed in routine clinical practice (i.e. majority of pre-menopausal patients presenting with T1c, node negative, ER+ invasive ductal carcinoma of intermediate grade).
2014-01-12 | E-GEOD-53958 | biostudies-arrayexpress
Project description:Background: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profi les of breast cancers and whether such profi les could be used to improve histologic grading. Methods: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. Results: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P<.001, log-rank test). Conclusions: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value. NB: The patients coming from Uppsala Hospital have been also used in other studies as in GSE3494. You can find the common set of patients in removing the abbreviation "UPP_" from the sample names and compare the results with the "INDEX (ID)" from the GSE3494 series. Experiment Overall Design: 64 microarray experiments from primary breast tumors used as training set to identify genes differentially expressed in grade 1 and 3. Experiment Overall Design: 129 microarray experiments from primary breast tumors of untreated patients used as validation set to validate the list of genes and its correlation with survival. Experiment Overall Design: No replicate, no reference sample. **NOTE** There are some inconsistencies between the sample annotation provided by GEO for this experiment in the GSE2990_family.soft.gz file and the supplementary data file GSE2990_suppl_info.txt. ***
2008-06-13 | E-GEOD-2990 | biostudies-arrayexpress
Project description:Based on fuzzy logic selection and classification algorithms, our selection method measures the contribution of each gene for each of two pre-defined classes in order to find the best discrimination. This algorithm extracts and ranks the most pertinent markers, since it is based on feature weighting according to optimal error rate, sensitivity and specificity. We applied the fuzzy logic selection on four breast cancer microarray databases to obtain new gene signatures based on histological grade. To validate these gene signatures, we designed probes for the selected genes on Nimblegen custom microarrays and tested them on a series of 151 consecutive invasive breast carcinomas displaying clinicopathological features similar to those observed in routine practice.
2014-01-12 | GSE53958 | GEO
Project description:Breast cancer was one of the first cancer types where molecular subtyping led to explanation of interpersonal heterogeneity and resulted in improvement of treatment regimen. Several multigene classifiers have been developed and in particular those defining molecular signatures of early breast cancers possess significant prognostic information. Hence since 2014, molecular subtyping of primary breast cancers was implemented as a part of routine diagnostics with direct impact of therapy assignment. In this study, we evaluate direct and potential benefits of molecular subtyping in low-risk breast cancers as well as present the advantages of a robust molecular signature in regard to patient work-up among high-risk breast cancers.
2017-12-01 | E-MTAB-5724 | biostudies-arrayexpress
Project description:Background: Histologic grade in breast cancer provides clinically important prognostic information. However, 30%-60% of tumors are classified as histologic grade 2. This grade is associated with an intermediate risk of recurrence and is thus not informative for clinical decision making. We examined whether histologic grade was associated with gene expression profi les of breast cancers and whether such profi les could be used to improve histologic grading. Methods: We analyzed microarray data from 189 invasive breast carcinomas and from three published gene expression datasets from breast carcinomas. We identified differentially expressed genes in a training set of 64 estrogen receptor (ER)-positive tumor samples by comparing expression profiles between histologic grade 3 tumors and histologic grade 1 tumors and used the expression of these genes to define the gene expression grade index. Data from 597 independent tumors were used to evaluate the association between relapse-free survival and the gene expression grade index in a Kaplan-Meier analysis. All statistical tests were two-sided. Results: We identified 97 genes in our training set that were associated with histologic grade; most of these genes were involved in cell cycle regulation and proliferation. In validation datasets, the gene expression grade index was strongly associated with histologic grade 1 and 3 status; however, among histologic grade 2 tumors, the index spanned the values for histologic grade 1-3 tumors. Among patients with histologic grade 2 tumors, a high gene expression grade index was associated with a higher risk of recurrence than a low gene expression grade index (hazard ratio = 3.61, 95% confidence interval = 2.25 to 5.78; P<.001, log-rank test). Conclusions: Gene expression grade index appeared to reclassify patients with histologic grade 2 tumors into two groups with high versus low risks of recurrence. This approach may improve the accuracy of tumor grading and thus its prognostic value. NB: The patients coming from Uppsala Hospital have been also used in other studies as in GSE3494. You can find the common set of patients in removing the abbreviation "UPP_" from the sample names and compare the results with the "INDEX (ID)" from the GSE3494 series. Keywords: disease state analysis
2006-02-16 | GSE2990 | GEO
Project description:When making treatment decisions, oncologists often stratify breast cancers into a low-risk group (ER+, low grade); an intermediate-risk group (ER+, high grade); and a high-risk group that includes Her2+ and triple-negative (ER-/PR-/Her2-) tumors. None of the currently available gene signatures correlates to this clinical classification. We aimed to develop a test that is practical for the oncologists, that offers both molecular characterization of BCs, and improved prediction of prognosis and treatment response. We investigated the molecular basis of such clinical practice by grouping Her2+ and triple-negative breast cancers together during clustering analyses on the genome-wide gene expression profiles of our training cohort, mostly derived from fine needle aspiration biopsies (FNABs) of 149 consecutive evaluable Breast cancers. The analyses consistently divided these tumors into a three-cluster pattern, similar to clinical risk-stratification groups, that was reproducible in published microarray databases (n=2487) annotated with clinical outcomes. The clinicopathologic parameters of each of these three molecular groups were also similar to clinical classification. The low-risk group had good outcomes and benefited from endocrine therapy. Both intermediate- and high-risk groups had poor outcomes and were resistant to endocrine therapy. The latter demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in MYC, E2F1, Ras, β-Catenin and IFN-γ pathways; and poor prognosis predicted by 14 independent prognostic signatures. Based on a multivariate analysis, this new gene signature, termed ClinicoMolecular Triad Classification, predicted recurrence and treatment response better than all pathologic parameters and other prognostic signatures. 149 invasive breast cancers from the 172 specimens contained 161 tumors were used in this study. Expression data of the 11 tumors with replicate was separately combined before analysis.
2011-09-28 | E-GEOD-16987 | biostudies-arrayexpress
Project description:In this study, using microarray technology we did a transcriptome profiling of miRNAs on a group of 52 cases of familial (BRCA1- or BRCA2-mutated, or BRCAX, i.e. familial cases with no mutations in BRCA1 or BRCA2 genes) and sporadic breast cancers. Class comparison of different clinical characteristics of the samples identified miR-342 as the miRNA with the most significant association with estrogen receptor (ER) status (categorised as positive and negative) of the samples analysed. As ER is one of the bio-pathological features currently used in routine clinical practice to aid treatment decision in breast cancer, identification of this miRNA has been promising for finding new mechanisms involved in this tumour type as we had next demonstrated in a cellular model of breast cancer.
2014-05-14 | GSE46966 | GEO
Project description:When making treatment decisions, oncologists often stratify breast cancers into a low-risk group (ER+, low grade); an intermediate-risk group (ER+, high grade); and a high-risk group that includes Her2+ and triple-negative (ER-/PR-/Her2-) tumors. None of the currently available gene signatures correlates to this clinical classification. We aimed to develop a test that is practical for the oncologists, that offers both molecular characterization of BCs, and improved prediction of prognosis and treatment response. We investigated the molecular basis of such clinical practice by grouping Her2+ and triple-negative breast cancers together during clustering analyses on the genome-wide gene expression profiles of our training cohort, mostly derived from fine needle aspiration biopsies (FNABs) of 149 consecutive evaluable Breast cancers. The analyses consistently divided these tumors into a three-cluster pattern, similar to clinical risk-stratification groups, that was reproducible in published microarray databases (n=2487) annotated with clinical outcomes. The clinicopathologic parameters of each of these three molecular groups were also similar to clinical classification. The low-risk group had good outcomes and benefited from endocrine therapy. Both intermediate- and high-risk groups had poor outcomes and were resistant to endocrine therapy. The latter demonstrated the highest rate of complete pathological response to neoadjuvant chemotherapy; the highest activities in MYC, E2F1, Ras, β-Catenin and IFN-γ pathways; and poor prognosis predicted by 14 independent prognostic signatures. Based on a multivariate analysis, this new gene signature, termed ClinicoMolecular Triad Classification, predicted recurrence and treatment response better than all pathologic parameters and other prognostic signatures.
2011-09-29 | GSE16987 | GEO