Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA340444 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Clinically annotated GEPs of 366 primary resected breast tumors ranked by a 12 gene chemokine score
2017-12-31 | GSE86166 | GEO
Project description:Molecular prognostic assays, such as Oncotype DX, are increasingly incorporated into the management of patients with invasive breast carcinoma. BreastPRS is a new molecular assay developed and validated from a meta-analysis of publically available genomic datasets. We applied the assay to matched fresh-frozen (FF) and formalin-fixed paraffin embedded (FFPE) tumor samples to translate the assay to FFPE. A linear relationship of the BreastPRS prognostic score was observed between tissue preservation formats. BreastPRS recurrence scores were compared with Oncotype DX recurrence scores from 246 patients with invasive breast carcinoma and known Oncotype DX results. Using this series, a 120-gene linear discriminant algorithm (LDA) was trained to predict Oncotype DX risk groups and then applied to series of untreated, node-negative, estrogen receptor (ER) – positive patients from previously published studies with known clinical outcomes. Correlation of recurrence score and risk group between Oncotype DX and BreastPRS was statistically significant (P<0.0001). 59 of 260 (23%) patients from four previously published studies were classified as intermediate-risk when the 120-gene LDA was applied. BreastPRS reclassified the 59 patients into binary risk groups (high vs. low-risk). 23 (39%) patients were classified as low-risk 36 (61%) as high-risk [P=0.029, HR: 3.64, 95% CI: 1.40 to 9.50]. At 10 years from diagnosis, the low-risk group had a 90% recurrence-free survival (RFS) rate, compared to 60% for the high-risk group. BreastPRS recurrence score is comparable to Oncotype DX and can reclassify Oncotype DX intermediate-risk patients into two groups with significant differences in RFS. Further studies are needed to validate these findings. Expression profiles of 246 invasive breast carcinomas.
2013-06-23 | E-GEOD-47109 | biostudies-arrayexpress
Project description:Background The dramatic increase in incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has given emphasis to the challenges of managing this important clinical entity. Unlike invasive breast cancer, there is no established histopathologic grading system for DCIS, nor are there biological markers of prognosis to guide clinical management. The aim of this study is to use molecular profiling to identify robust and clinically applicable indicators of DCIS malignant potential. Methods Areas of intraduct carcinoma, atypical ductal hyperplasia and benign epithelium were isolated from 46 well-characterised invasive breast cancers by laser capture microdissection. Microarray based gene expression profiling was used to identify genes differentially expressed between DCIS associated with grade 1 and grade 3 invasive carcinoma (‘grade associated genes’). The expression profile of these genes was then determined in all samples and used to define ‘molecular grade’ categories. The genomic basis of gene expression derived categories was examined by array-based comparative genomic hybridisation (CGH). Results DCIS samples could be divided into two subgroups, designated low and high molecular grade (MG) on the basis of expression at 173 grade associated oligonucleotide probes. The low MG subgroup included 21 DCIS samples of low (n=10) and intermediate (n=11) nuclear grade as well as all samples of ADH (n=4) and benign epithelium (n=7). The high MG subgroup included 27 DCIS samples of intermediate (n=7) and high (n=19) nuclear grade. Array CGH revealed distinct differences in the character and degree of genomic aberration associated with MG and the clinical significance of MG was verified by a strong correlation with survival in two independent invasive breast cancer gene expression datasets (n=295 and n=186). MG categories were strongly associated with histopathologic and biomarker features of DCIS. Using a classification tree model, DCIS MG could be accurately predicted in 44/46 (95.7%) of samples using a combination of nuclear grade and Ki67 score. Conclusions Molecular profiling indicates a binary grading scheme for DCIS that is both biologically relevant and clinically informative. The low and high MG DCIS classification could be recapitulated by a novel combination of routinely accessible features. This practical approach has potential to immediately improve clinical evaluation and management of DCIS. Keywords: Paired gene expression and CGH Paired CGH and Gene Expression on DCIS of the breast
2008-11-24 | E-GEOD-7882 | biostudies-arrayexpress
Project description:Molecular prognostic assays, such as Oncotype DX, are increasingly incorporated into the management of patients with invasive breast carcinoma. BreastPRS is a new molecular assay developed and validated from a meta-analysis of publically available genomic datasets. We applied the assay to matched fresh-frozen (FF) and formalin-fixed paraffin embedded (FFPE) tumor samples to translate the assay to FFPE. A linear relationship of the BreastPRS prognostic score was observed between tissue preservation formats. BreastPRS recurrence scores were compared with Oncotype DX recurrence scores from 246 patients with invasive breast carcinoma and known Oncotype DX results. Using this series, a 120-gene linear discriminant algorithm (LDA) was trained to predict Oncotype DX risk groups and then applied to series of untreated, node-negative, estrogen receptor (ER) – positive patients from previously published studies with known clinical outcomes. Correlation of recurrence score and risk group between Oncotype DX and BreastPRS was statistically significant (P<0.0001). 59 of 260 (23%) patients from four previously published studies were classified as intermediate-risk when the 120-gene LDA was applied. BreastPRS reclassified the 59 patients into binary risk groups (high vs. low-risk). 23 (39%) patients were classified as low-risk 36 (61%) as high-risk [P=0.029, HR: 3.64, 95% CI: 1.40 to 9.50]. At 10 years from diagnosis, the low-risk group had a 90% recurrence-free survival (RFS) rate, compared to 60% for the high-risk group. BreastPRS recurrence score is comparable to Oncotype DX and can reclassify Oncotype DX intermediate-risk patients into two groups with significant differences in RFS. Further studies are needed to validate these findings.
2013-06-23 | GSE47109 | GEO
Project description:Background: Breast cancer is a heterogeneous neoplasm. Distinct subtypes of breast cancer have been defined, suggesting the existence of molecular differences contributing to their clinical outcomes. However, the molecular differences between HER2 positive and negative breast cancer tumors remain unclear. Objective: The aim of this study was to identify a gene expression profile for breast tumors based on HER2 status. Material and methods: The HER2 status was determined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 54 breast tumor samples. Using Affymetrix microarray data from these breast tumors, we established the expression profiling of breast cancer based on HER2 IHC and FISH results. To validate microarray experiment data, real-time quantitative reverse transcription-PCR was performed. Results: We found significant differences between the HER2-positive and HER2-negative breast tumor samples, which included overexpression of HER2, as well as other genes located on 17q12, and genes functionally related to migration. Conclusion: Our study shows the potential of integrated genomics profiling to shed light on the molecular knowledge of HER2-positive breast tumors. The tumor samples under study correspond to 54 primary breast carcinomas. They included 15 cases with a HER2 IHC3+ score with HER2 gene amplification, 13 cases with IHC2+ score with amplification and 13 without HER2 gene amplification, and 13 cases IHC0/1+ score without HER2 gene amplification. 12 samples of breast normal tissues from breast cancer patients were also included as a reference. Neither overexpression nor amplification of HER2 was observed.
2011-12-22 | E-GEOD-29431 | biostudies-arrayexpress
Project description:Background The dramatic increase in incidence of ductal carcinoma in situ (DCIS) associated with mammographic screening for breast cancer has given emphasis to the challenges of managing this important clinical entity. Unlike invasive breast cancer, there is no established histopathologic grading system for DCIS, nor are there biological markers of prognosis to guide clinical management. The aim of this study is to use molecular profiling to identify robust and clinically applicable indicators of DCIS malignant potential. Methods Areas of intraduct carcinoma, atypical ductal hyperplasia and benign epithelium were isolated from 46 well-characterised invasive breast cancers by laser capture microdissection. Microarray based gene expression profiling was used to identify genes differentially expressed between DCIS associated with grade 1 and grade 3 invasive carcinoma (‘grade associated genes’). The expression profile of these genes was then determined in all samples and used to define ‘molecular grade’ categories. The genomic basis of gene expression derived categories was examined by array-based comparative genomic hybridisation (CGH). Results DCIS samples could be divided into two subgroups, designated low and high molecular grade (MG) on the basis of expression at 173 grade associated oligonucleotide probes. The low MG subgroup included 21 DCIS samples of low (n=10) and intermediate (n=11) nuclear grade as well as all samples of ADH (n=4) and benign epithelium (n=7). The high MG subgroup included 27 DCIS samples of intermediate (n=7) and high (n=19) nuclear grade. Array CGH revealed distinct differences in the character and degree of genomic aberration associated with MG and the clinical significance of MG was verified by a strong correlation with survival in two independent invasive breast cancer gene expression datasets (n=295 and n=186). MG categories were strongly associated with histopathologic and biomarker features of DCIS. Using a classification tree model, DCIS MG could be accurately predicted in 44/46 (95.7%) of samples using a combination of nuclear grade and Ki67 score. Conclusions Molecular profiling indicates a binary grading scheme for DCIS that is both biologically relevant and clinically informative. The low and high MG DCIS classification could be recapitulated by a novel combination of routinely accessible features. This practical approach has potential to immediately improve clinical evaluation and management of DCIS. Keywords: Paired gene expression and CGH
2008-11-24 | GSE7882 | GEO
Project description:Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting.
2017-07-16 | GSE72254 | GEO
Project description:Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting.
2017-07-16 | GSE72251 | GEO
Project description:Breast cancer (BC) is one of the most common and deadliest malignancies in women worldwide. Tumor immune response is increasingly recognized to be associated with better clinical outcome in breast and other cancers. However, the quantitative evaluation of the tumor immune response by measuring tumor-infiltrating lymphocytes (TILs) remains challenging, since it relies on subjective measurements, which are limited in accuracy and reproducibility. In this study, we sought to identify a set of DNA methylation markers (MeTIL signature) that better recapitulate the evaluation of TILs and their impact on long-term outcome in BC. We showed that the MeTIL score measures TIL distributions in a more robust and sensitive manner than conventional pathological TIL counts and that this translates into better prediction of survival and response to chemotherapy in BC. We demonstrated that the MeTIL score can be determined in low amounts of DNA from FFPE tumor tissue by bisulfite pyrosequencing allowing for the fast and cost-efficient evaluation of TILs in the clinical setting.
2017-07-16 | GSE72245 | GEO