Pivotal role of HMGA1 gene signature in highly metastatic breast cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Pegoraro S
PROVIDER: S-ECPF-GEOD-35525 | biostudies-other | 2013 Aug
REPOSITORIES: biostudies-other
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Project description:Analysis of MDA-MB-231 breast cancer cells depleted for High Mobility Group A1 (HMGA1) using siRNA. HMGA1 is involved in invasion and metastasis in breast cancer cells. Results identify the specific transcriptional program induced by HMGA1 in highly metastatic breast cancer cells.
2013-12-10 | GSE35525 | GEO
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2016-03-30 | E-GEOD-67675 | biostudies-arrayexpress
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).
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2016-03-30 | GSE67675 | GEO
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