Blood mRNA expression of REV3L and TYMS as potential predictive biomarkers from platinum-based chemotherapy plus pemetrexed in non-small cell lung cancer patients

Autor: M. Teresa Agulló-Ortuño, Luis Paz-Ares, Lara Iglesias, Virginia Pardo-Marqués, Juan A. Núñez, Jon Zugazagoitia, Inmaculada García-Ruiz, C. Vanesa Díaz-García, Jose A. Lopez-Martin, Elena Prieto-García, Ana Belén Enguita, Santiago Ponce
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Lung Neoplasms
Organoplatinum Compounds
medicine.medical_treatment
Gene Expression
DNA-Directed DNA Polymerase
Toxicology
Thymidylate synthase
0302 clinical medicine
REV3L
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
Medicine
Pharmacology (medical)
Prospective Studies
Aged
80 and over
Gene knockdown
biology
Middle Aged
Progression-Free Survival
DNA-Binding Proteins
Pemetrexed
030220 oncology & carcinogenesis
Female
medicine.drug
medicine.medical_specialty
03 medical and health sciences
Internal medicine
Biomarkers
Tumor
Humans
Gene silencing
Gene Silencing
RNA
Messenger
Lung cancer
Aged
Cell Proliferation
Pharmacology
Chemotherapy
business.industry
Cancer
Thymidylate Synthase
medicine.disease
030104 developmental biology
biology.protein
business
Zdroj: Cancer Chemotherapy and Pharmacology. 85:525-535
ISSN: 1432-0843
0344-5704
DOI: 10.1007/s00280-019-04008-9
Popis: Therapeutic options for cancer patients have increased in the last years, although drugs resistance problem remains unresolved. Genetic background in individual susceptibility to cancer treatment could influence the therapy responses. The aim of this study was to explore the feasibility of using blood 4 genes (AEG-1, BRCA-1, REV3L and TYMS) expression levels as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer. Sixteen patients from the Medical Oncology Department at “12 de Octubre” Hospital, were included in the study. Total mRNA was isolated from blood samples, and gene expression was analyzed by RT-qPCR. A panel of lung tumor cell lines were used in cell proliferation tests and siRNA-mediated silencing assays. Similarity between blood gene expression levels and protein expression in matched tumor tissue was observed in 54.54% (REV3L) and 81.81% (TYMS) of cases. Gene expression of REV3L and TYMS in blood correlated directly and inversely, respectively, with progression-free survival and overall survival in the patients from our cohort. In tumor cell lines, the knockdown of REV3L conferred resistance to pemetrexed treatment, and the TYMS silencing increased the pemetrexed sensitivity of tumor cells. The use of peripheral blood samples for expression quantification of interest genes is an affordable method with promising results in the evaluation of response to pemetrexed treatment. Therefore, expression levels of REV3L and TYMS genes might be used as predictive biomarkers in advanced NSCLC patients.
Databáze: OpenAIRE
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