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

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgements

This work was supported by Fundación Mutua Madrileña (Madrid, Spain) [Grant Number 2013/0074].

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Authors and Affiliations

  1. Laboratory of Clinical and Translational Oncology, Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), Avda de Córdoba s/n, 28041, Madrid, Spain

    M. Teresa Agulló-Ortuño, Inmaculada García-Ruiz, C. Vanesa Díaz-García, Virginia Pardo-Marqués, Elena Prieto-García, José A. López-Martín & Luis Paz-Ares

  2. Lung Cancer Group, Clinical Research Program, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    M. Teresa Agulló-Ortuño, Santiago Ponce, Lara Iglesias, Jon Zugazagoitia, José A. López-Martín & Luis Paz-Ares

  3. Biomedical Research Networking Centre: Oncology (CIBERONC), Instituto de Salud Carlos III, C. Monforte de Lemos, 3, 28029, Madrid, Spain

    M. Teresa Agulló-Ortuño & Luis Paz-Ares

  4. Pathology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba s/n, 28041, Madrid, Spain

    Ana B. Enguita

  5. Medical Oncology Department, Hospital Universitario 12 de Octubre, Avda de Córdoba s/n, 28041, Madrid, Spain

    Santiago Ponce, Lara Iglesias, Jon Zugazagoitia, José A. López-Martín, Luis Paz-Ares & Juan A. Nuñez

  6. Medicine Department, Facultad de Medicina y Cirugía, Universidad Complutense de Madrid (UCM), Avda de Séneca, 2, 28040, Madrid, Spain

    Luis Paz-Ares

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  1. M. Teresa Agulló-Ortuño
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  2. Inmaculada García-Ruiz
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Correspondence to M. Teresa Agulló-Ortuño.

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Agulló-Ortuño, M.T., García-Ruiz, I., Díaz-García, C.V. et al. Blood mRNA expression of REV3L and TYMS as potential predictive biomarkers from platinum-based chemotherapy plus pemetrexed in non-small cell lung cancer patients. Cancer Chemother Pharmacol 85, 525–535 (2020). https://doi.org/10.1007/s00280-019-04008-9

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