Dataset Information

Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.

ABSTRACT:

Background

Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm.

Methodology/principal findings

By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathways of previously described carcinoma-derived mesenchymal tumor cells (A17) with that of both carcinomas and other mesenchymal phenotypes, such as mesenchymal stem cells (MSCs), breast stroma, and various types of sarcomas. We identified three mesenchymal/stromal-signatures which A17 cells shares with MSCs and breast stroma. By using a recently developed computational approach with publicly available microarray data, we show that these signatures: 1) significantly relates to basal-like breast cancer subtypes; 2) significantly relates to bone metastasis; 3) are up-regulated after hormonal treatment; 4) predict resistance to neoadjuvant therapies.

Conclusions/significance

Our results demonstrate that mesenchymalization is an intrinsic property of the most aggressive tumors and it relates to therapy resistance as well as bone metastasis.

SUBMITTER: Marchini C

PROVIDER: S-EPMC2994727 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Publications

Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.

Marchini Cristina C Montani Maura M Konstantinidou Georgia G Orrù Rita R Mannucci Silvia S Ramadori Giorgio G Gabrielli Federico F Baruzzi Anna A Berton Giorgio G Merigo Flavia F Fin Stefania S Iezzi Manuela M Bisaro Brigitte B Sbarbati Andrea A Zerani Massimo M Galiè Mirco M Amici Augusto A

PloS one 20101130 11

<h4>Background</h4>Mounting clinical and experimental evidence suggests that the shift of carcinomas towards a mesenchymal phenotype is a common paradigm for both resistance to therapy and tumor recurrence. However, the mesenchymalization of carcinomas has not yet entered clinical practice as a crucial diagnostic paradigm.<h4>Methodology/principal findings</h4>By integrating in silico and in vitro studies with our epithelial and mesenchymal tumor models, we compare herein crucial molecular pathw ...[more]

PMID: 21152434

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Project description:BackgroundAcute myeloid leukemia (AML) is a highly heterogenous disease with varying clinical outcomes among patients. Epithelial-mesenchymal transition (EMT) is an important mechanism underlying cancer metastasis and chemotherapy resistance. However, few EMT-based signatures have been established to predict AML prognosis and treatment efficacy.MethodsBy conducting comparative RNA-seq analysis, we discovered the differential expression of EMT genes between AML patients with relapse and those without relapse. Based on the prognostic analysis of the differentially expressed EMT genes, a metastasis-related EMT signature (MEMTs) was constructed. An analysis was conducted on both TARGET and TCGA cohorts to explore the possible association between MEMTs and prognosis in AML. Three separate chemotherapy treatment cohorts were utilized to assess the predictive efficacy of MEMTs for chemotherapy response. In addition, the potential correlation between MEMTs and the tumor microenvironment was also investigated. Finally, random forest analysis and functional experiments were conducted to verify the key MEMTs gene associated with AML metastasis.ResultsBased on expression and prognostic analysis, we constructed MEMTs that include three EMT genes (CDH2, LOX, and COL3A1). Our findings suggested that the MEMTs could act as a prognostic factor for AML patients, and furthermore, it proved to be a predictor of their response to chemotherapy. Specifically, high MEMTs was associated with worse prognosis and poor response to chemotherapy, while low MEMTs was linked to better prognosis and higher response rates. Random forest and functional experiments demonstrate that CDH2 is a key gene promoting leukemia cell metastasis among the three MEMTs genes.ConclusionThe identification of MEMTs could potentially act as a predictor for the prognosis and the response to chemotherapy in AML patients. Individual tumor evaluation based on MEMTs could provide personalized treatment options for AML patients in the future.

Dataset Information

Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.

Background

Methodology/principal findings

Conclusions/significance

Publications

Mesenchymal/stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies.

Similar Datasets

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