Abstract
BackgroundAlthough 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.MethodsSixty-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.ResultsTYMS 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).ConclusionsTYMS 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.
Highlights
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
We evaluated the relationship between TYMS gene expression and clinical outcome in a cohort of 62 patients with advanced non-small cell lung cancer (NSCLC) treated with a pemetrexed-based regimen at our institution
TYMS gene expression in advanced tumors In order to assess the suitability of TYMS gene-expression measurement as a predictive marker of pemetrexed sensitivity in advanced NSCLC patients, we first quantitatively evaluated the TYMS gene-expression levels in samples from the 62 pemetrexed-treated patients in our series
Summary
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. In some cancer types, such as advanced NSCLC, this point is controversial For this reason, we evaluated the relationship between TYMS gene expression and clinical outcome in a cohort of 62 patients with advanced NSCLC treated with a pemetrexed-based regimen at our institution. QPCR is suitable for use with mRNA from archived formalin-fixed, paraffin-embedded (FFPE) samples, as it amplifies
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