1. Splicing factor ratio as an index of epithelial-mesenchymal transition and tumor aggressiveness in breast cancer
- Author
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Anne Pierre Morel, Laura Mercatali, Emanuela Scarpi, Pietro Fici, Michel Rigaud, Toni Ibrahim, Dino Amadori, Francesco Fabbri, Giulia Gallerani, Alain Puisieux, Fici P., Gallerani G., Morel A.-P., Mercatali L., Ibrahim T., Scarpi E., Amadori D., Puisieux A., Rigaud M., and Fabbri F.
- Subjects
0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,tumor aggressiveness ,Tumor aggressivene ,Epithelial-Mesenchymal Transition ,Prognosi ,Breast Neoplasms ,RNA-Binding Protein ,Metastasis ,03 medical and health sciences ,Breast cancer ,EMT ratio ,Internal medicine ,Cell Line, Tumor ,Early prediction ,medicine ,Biomarkers, Tumor ,Humans ,Epithelial–mesenchymal transition ,early breast cancer ,Early breast cancer ,Aged ,Aged, 80 and over ,business.industry ,EMT ,Cancer ,RNA-Binding Proteins ,Middle Aged ,medicine.disease ,Prognosis ,Primary tumor ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,RNA Splicing Factor ,Alternative Splicing ,030104 developmental biology ,Tumor progression ,Female ,RNA Splicing Factors ,Neoplasm Grading ,business ,Breast Neoplasm ,Human ,Research Paper - Abstract
// Pietro Fici 1 , Giulia Gallerani 1 , Anne-Pierre Morel 2, 3, 4, 5, 6 , Laura Mercatali 7 , Toni Ibrahim 7 , Emanuela Scarpi 8 , Dino Amadori 9 , Alain Puisieux 2, 3, 4, 5, 6, 10 , Michel Rigaud 1 , Francesco Fabbri 1 1 Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy 2 Inserm UMR-S1052, Centre de Recherche en Cancerologie de Lyon, Lyon, France 3 CNRS UMR5286, Centre de Recherche en Cancerologie de Lyon, Lyon, France 4 Centre Leon Berard, Lyon, France 5 UNIV UMR1052, Lyon, France 6 Universite de Lyon, Lyon, France 7 Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy 8 Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy 9 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy 10 Institut Universitaire de France, Paris, France Correspondence to: Pietro Fici, email: pietro.fici@irst.emr.it Keywords: EMT, early breast cancer, tumor aggressiveness, alternative splicing, EMT ratio Received: May 10, 2016 Accepted: November 21, 2016 Published: November 29, 2016 ABSTRACT Epithelial-to-mesenchymal transition (EMT) has been shown to be associated with tumor progression and metastasis. During this process in breast cancer, a crucial role is played by alternative splicing systems. To identify a new early prognostic marker of metastasis, we evaluated EMT-related gene expression in breast cell lines, and in primary tumor tissue from 31 patients with early breast cancer, focusing our attention on EMT-related splicing factors ESRP1, ESRP2 and RBFOX2. Results showed that the expression patterns of these genes were indicative of the onset of EMT in in-vitro models, but not in tissue samples. However, the ratio between ESRP1 or ESRP2 and RBFOX2 significantly decreased during EMT and positively correlated with the EMT-specific phenotype in cell models, representing a promising prognostic markers. Low ESRP1/RBFOX2 ratio value was associated with a higher risk of metastasis ( p < 0.005) in early breast cancer patients, regardless other clinical features. A cut-off of ratio of 1.067 was determined by ROC curve analysis (AUC 0.8375; 95% CI 0.6963–0.9787). Our study show evidence that a decrease in this ratio correlates with cancer progression. The results provide a rationale for using ESRP1/RBFOX2 ratio as a new prognostic biomarker for the early prediction of metastatic potential in breast cancer.
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- 2016