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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Pulmonary Medicine 1/2015

Thymidylate synthase expression as a predictive biomarker of pemetrexed sensitivity in advanced non-small cell lung cancer

Zeitschrift:
BMC Pulmonary Medicine > Ausgabe 1/2015
Autoren:
Cristina Chamizo, Sandra Zazo, Manuel Dómine, Ion Cristóbal, Jesús García-Foncillas, Federico Rojo, Juan Madoz-Gúrpide
Wichtige Hinweise

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

Conceived and designed the experiments: CC, JGF, FR. Selected the samples: MD. Collected patient’s clinical information: MD, CC, JMG. Performed the experiments: CC, SZ, IC. Analyzed the data: CC, JMG. Wrote the paper: JMG. All authors read and approved the final manuscript.

Abstract

Background

Although it has been suggested that a high level of thymidylate synthase (TYMS) gene expression in malignant tumors is related to reduced sensitivity to the antifolate drug pemetrexed, no direct evidence for such an association has been demonstrated in routine clinical samples from patients treated with the drug. The purpose of this study was to quantitatively assess the impact of TYMS gene expression in tumor cells as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer (NSCLC) treated at our institution.

Methods

Sixty-two NSCLC patients were included in this study: 16 patients received platins-pemetrexed as first-line NSCLC, and 46 pemetrexed in monotherapy as second- or subsequent-line treatment. Total mRNA was isolated and the expression of TYMS was analyzed by RT-qPCR. TYMS levels were calibrated against expression in normal lung tissue.

Results

TYMS overexpression was detected in 61 % of patients and low expression in 39 %. The response rate for patients with low TYMS expression was 0.29 compared with 0.03 in patients with overexpression (P = 0.025). A significant benefit was observed in patients with low expression both in time to progression (average TTP = 56 vs. 23 months, P = 0.001) and in overall survival (average OS = 60 vs. 25 months, P = 0.002).

Conclusions

TYMS overexpression in tumor cells correlated with a reduced response to pemetrexed-containing chemotherapy and might be used as a predictive biomarker in advanced NSCLC patients.
Literatur
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