Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide
0301 basic medicine
Cytotoxicity
Science
Datasets as Topic
Tretinoin
Kaplan-Meier Estimate
Real-Time Polymerase Chain Reaction
Renin-Angiotensin System
Inhibitory Concentration 50
03 medical and health sciences
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Humans
Computer Simulation
Precision Medicine
Etoposide
2. Zero hunger
0303 health sciences
Acute myeloid leukemia
Q
R
Cytarabine
Cancer drug discovery
Prognosis
3. Good health
Leukemia, Myeloid, Acute
Gene Ontology
Nonlinear Dynamics
Doxorubicin
Drug Resistance, Neoplasm
Medicine
Gene expression
Renin-angiotensin system
Linear regression analysis
Biomarkers
Research Article
DOI:
10.1371/journal.pone.0242497
Publication Date:
2020-11-25T18:24:34Z
AUTHORS (12)
ABSTRACT
Despite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.
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CITATIONS (20)
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