The knowledge of the structure, function, and abundance of specific proteins related to the EMT process is essential for developing effective diagnostic approaches to cancer with the perspective of diagnosis and therapy of malignancies. The success of all-trans retinoic acid (ATRA) differentiation therapy in acute promyelocytic leukemia has stimulated studies in the treatment of other tumors with ATRA. This review will discuss the impact of ATRA use, emphasizing epithelial-mesenchymal transition (EMT) proteins in breast cancer, of which metastasis and recurrence are major causes of death.

• Keywords
• ATRA, EMT, breast cancer, protein,
• MeSH
• Epithelial-Mesenchymal Transition * MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Neoplasm Proteins agonists   metabolism   MeSH
• Breast Neoplasms metabolism   mortality   pathology   MeSH
• Receptors, Retinoic Acid agonists   metabolism   MeSH
• Tretinoin metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Neoplasm Proteins MeSH
• Receptors, Retinoic Acid MeSH
• Tretinoin MeSH

The survival rate for patients with high-risk neuroblastomas remains poor despite new improvements in available therapeutic modalities. A detailed understanding of the mechanisms underlying clinical responses to multimodal treatment is one of the important aspects that may provide precision in the prediction of a patient's clinical outcome. Our study was designed as a detailed comparative analysis of five selected proteins (DDX39A, HMGA1, HOXC9, NF1, and PBX1) in one cohort of patients using the same methodical approaches. These proteins were already reported separately as related to the resistance or sensitivity to retinoids and as useful prognostic markers of survival probability. In the cohort of 19 patients suffering from high-risk neuroblastomas, we analyzed initial immunohistochemistry samples obtained by diagnostic biopsy and post-induction samples taken after the end of induction therapy. The expression of DDX39A, HMGA1, HOXC9, and NF1 showed varied patterns with almost no differences between responders and non-responders. Nevertheless, we found very interesting results for PBX1: non-responders had significantly higher expression levels of this protein in the initial tumor samples when compared with responders; this expression pattern changed inversely in the post-induction samples, and this change was also statistically significant. Moreover, our results from survival analyses reveal the prognostic value of PBX1, NF1, and HOXC9 expression in neuroblastoma tissue. In addition to the prognostic importance of PBX1, NF1, and HOXC9 proteins, our results demonstrated that PBX1 could be used for the prediction of the clinical response to induction chemotherapy in patients suffering from high-risk neuroblastoma.

• Keywords
• HOXC9, NF1, PBX1, immunohistochemistry, neuroblastoma, predictive markers, prognostic markers,
• Publication type
• Journal Article MeSH

Although the administration of retinoids represents an important part of treatment for children suffering from high-risk neuroblastomas, approximately 50% of these patients do not respond to this therapy or develop resistance to retinoids during treatment. Our study focused on the comparative analysis of the expression of five genes and corresponding proteins (DDX39A, HMGA1, HMGA2, HOXC9 and PBX1) that have recently been discussed as possible predictive biomarkers of clinical response to retinoid differentiation therapy. Expression of these five candidate biomarkers was evaluated at both the mRNA and protein level in the same subset of 8 neuroblastoma cell lines after treatment with natural or synthetic retinoids. We found that the cell lines that were HMGA2-positive and/or HOXC9-negative have a reduced sensitivity to retinoids. Furthermore, the experiments revealed that the retinoid-sensitive cell lines showed a uniform pattern of change after treatment with both natural and sensitive retinoids: increased DDX39A and decreased PBX1 protein levels. Our results showed that in NBL cells, these putative protein biomarkers are associated with sensitivity or resistance to retinoids, and their endogenous or induced expression can distinguish between these two phenotypes.

• MeSH
• Bexarotene pharmacology   MeSH
• Biomarkers, Pharmacological metabolism   MeSH
• Drug Resistance, Neoplasm drug effects   genetics   MeSH
• DEAD-box RNA Helicases genetics   metabolism   MeSH
• Child MeSH
• Fenretinide pharmacology   MeSH
• Tissue Fixation MeSH
• Homeodomain Proteins genetics   metabolism   MeSH
• Isotretinoin pharmacology   MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Cell Line, Tumor MeSH
• Nervous System Neoplasms genetics   metabolism   pathology   surgery   MeSH
• Neuroblastoma genetics   metabolism   pathology   surgery   MeSH
• Infant, Newborn MeSH
• Pre-B-Cell Leukemia Transcription Factor 1 genetics   metabolism   MeSH
• Child, Preschool MeSH
• Cell Proliferation drug effects   MeSH
• HMGA1a Protein genetics   metabolism   MeSH
• HMGA2 Protein genetics   metabolism   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Tretinoin analogs & derivatives   pharmacology   MeSH
• Paraffin Embedding MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 9,13-retinoic acid MeSH Browser
• Bexarotene MeSH
• Biomarkers, Pharmacological MeSH
• DDX39A protein, human MeSH Browser
• DEAD-box RNA Helicases MeSH
• Fenretinide MeSH
• HMGA2 protein, human MeSH Browser
• Homeodomain Proteins MeSH
• Hoxc9 protein, human MeSH Browser
• Isotretinoin MeSH
• PBX1 protein, human MeSH Browser
• Pre-B-Cell Leukemia Transcription Factor 1 MeSH
• HMGA1a Protein MeSH
• HMGA2 Protein MeSH
• Antineoplastic Agents MeSH
• Tretinoin MeSH