Alterations of the MEK/ERK, BMP, and Wnt/β-catenin pathways detected in the blood of individuals with lymphatic malformations
| Autor: | Ramrada Lekwuttikarn, Kavita Y. Sarin, Joyce M.C. Teng, Jiang Li, Elidia Tafoya, Taehan Kim, Malcolm P. Chelliah |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male Metabolic Processes Physiology Gene Expression Pathogenesis Pathology and Laboratory Medicine Biochemistry Oxidative Phosphorylation 0302 clinical medicine Drug Discovery Medicine and Health Sciences Medicine Child Wnt Signaling Pathway Multidisciplinary Pharmaceutics Wnt signaling pathway Healthy Volunteers 3. Good health Body Fluids Lymphatic system Blood 030220 oncology & carcinogenesis Child Preschool Bone Morphogenetic Proteins Female Metabolic Pathways Anatomy Research Article Drug Research and Development Adolescent MAP Kinase Signaling System Science Bone morphogenetic protein 03 medical and health sciences Young Adult Drug Therapy Gene Types Genetics Humans Gene Regulation PI3K/AKT/mTOR pathway Pharmacology Lymphatic Abnormalities business.industry Sequence Analysis RNA Gene Expression Profiling Biology and Life Sciences Gene signature 030104 developmental biology Metabolism Catenin Case-Control Studies Cancer research Regulator Genes business Transcriptome |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 4, p e0213872 (2019) |
| ISSN: | 1932-6203 |
| Popis: | Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/β-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. |
| Databáze: | OpenAIRE |
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