Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia

Autor: Peyman Eshghi, Nasrin Dehghan-Nayeri, Mir Davood Omrani, Kourosh Goudarzi Pour, Mostafa Rezaei-Tavirani, Ahmad Gharehbaghian
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Proteomics
Cancer Research
Antineoplastic Agents
Hormonal
medicine.medical_treatment
Purine nucleoside phosphorylase
Biology
Toxicology
Real-Time Polymerase Chain Reaction
Dexamethasone
03 medical and health sciences
0302 clinical medicine
Therapeutic index
Cell Line
Tumor
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
medicine
Biomarkers
Tumor
Humans
Pharmacology (medical)
RNA
Messenger
Child
Cell Proliferation
Pharmacology
Chemotherapy
Activator (genetics)
Infant
medicine.disease
Prognosis
Molecular biology
Gene Expression Regulation
Neoplastic
Leukemia
030104 developmental biology
Oncology
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Child
Preschool
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Cancer cell
Cancer research
Protein Expression Analysis
Female
medicine.drug
Zdroj: Cancer chemotherapy and pharmacology. 80(1)
ISSN: 1432-0843
Popis: Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE-MALDI-TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.
Databáze: OpenAIRE
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