Unknown,Transcriptomics,Genomics,Proteomics

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MicroRNA expression profiling of early primary breast cancer to identify prognostic markers and associated pathways

ABSTRACT: Retrospective series of primary breast cancer patients who received surgery between 1989 and 1992. Patients received adjuvant chemotherapy and/or adjuvant hormone therapy, or no adjuvant treatment. Tamoxifen was used as endocrine therapy for 5 years in ER+ BC patients. Patients who were <50 years of age, with lymph node positive tumors, or ER– and/or >3 cm in diameter, received adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) for six cycles, in a thrice weekly intravenous regimen. Patients >50 years of age with ER–, lymph node–positive tumors also received CMF. Retrospective clinical study to identify breast cancer prognostic markers and associated pathways. 210 early primary breast cancers were considered who had complete 10-years follow-up, clinical and demographics information. miRNA profiling data.

ORGANISM(S): Homo sapiens

SUBMITTER: Francesca Buffa

PROVIDER: E-GEOD-22216 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

microRNA-associated progression pathways and potential therapeutic targets identified by integrated mRNA and microRNA expression profiling in breast cancer.

Buffa Francesca M FM Camps Carme C Winchester Laura L Snell Cameron E CE Gee Harriet E HE Sheldon Helen H Taylor Marian M Harris Adrian L AL Ragoussis Jiannis J

Cancer research 20110707 17

microRNA expression profiling plays an emerging role in cancer classification and identification of therapeutic strategies. In this study, we have evaluated the benefits of a joint microRNA-mRNA analysis in breast cancer. Matched mRNA and microRNA global expression profiling was conducted in a well-annotated cohort of 207 cases with complete 10-year follow-up. Penalized Cox regression including microRNA expression, mRNA expression, and clinical covariates was used to identify microRNAs associate ...[more]

PMID: 21737487

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Project description:Background Currently, no gene-expression signature (GES) established from node-positive cohorts, able to predict breast cancer evolution after systemic adjuvant chemotherapy, exists. Methods Gene-expression profiles of 252 node-positive patients (median follow-up: 7.7 years), mostly included in a randomized clinical trial (PACS01), receiving systemic adjuvant regimen, were determined by means of cDNA custom array representing 5,776 distinct genes. Findings In the training cohort, we established a 38-GES for the purpose of predicting time to distant metastasis. The 38-GES yielded unadjusted hazard ratio of 4.86 (95% CI=2.76-8.56). Even when adjusted with the two best clinicopathological prognostic scoring: NPI and Adjuvant!, 38-GES HR were 3.30 (1.81-5.99) and 3.40 (1.85-6.24), respectively. Furthermore, 38-GES improved mostly NPI and Adjuvant! intermediate-risk classified patients. NPI intermediate-risk patients (7-year MFS=87.2%) were divided into 2/3 (7-year MFS=95.5%) close to NPI low-risk group and 1/3 (7-year MFS=69.3%) close to NPI high-risk group (HR=6.97 [2.51-19.36]). Adjuvant! intermediate-risk patients (7-year MFS=88.0%) were divided into 2/3 (7-year MFS=94.8%) close to Adjuvant! low-risk group and 1/3 (7-year MFS=71.7%) close to Adjuvant! high-risk group (HR=5.31 [5.38-11.87]). The 38-GES was validated on gene-expression datasets from three external node-positive breast cancer subcohorts (n=224) generated from different microarray platforms. The 38-GES yielded unadjusted HR=2.95 (1.74-5.01). Furthermore, 38-GES showed performance in supplementary cohorts with different lymph-node status and endpoint (1,031 new patients). Interpretation The 38-GES represents a robust tool able to type systemic adjuvant treated node-positive patients at high risk of metastatic relapse, and especially powerful to separate NPI or Adjuvant! intermediate-risk node-positive patients. Keywords: disease-state analysis 252 breast cancer patients at diagnosis examined with spotted cDNA nylon membrane. Patient details: PACS01x are 2 parts of a clinical trial : PACS01A : patients had received 6 cycles of FEC100 PACS01B : patients had received 3 cycles of FEC100 then 3 cycles of Docetaxel CCRG are patients from our local cancer center (Cancer Center René Gauducheau) included with the same criteria as PACS01A (6 cycles of FEC100).

Dataset Information

MicroRNA expression profiling of early primary breast cancer to identify prognostic markers and associated pathways

Publications

microRNA-associated progression pathways and potential therapeutic targets identified by integrated mRNA and microRNA expression profiling in breast cancer.

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