Abstract 2263: Prognostic significance of REV3like and TYMS gene expression in blood samples from non-small cell lung patients treated with platinum-based chemotherapy plus pemetrexed
Authors: Agullo-Ortuño Maria Teresa , Díaz-García C.Vanessa , López-Martín José A. , Prieto-García Elena , Ponce Santiago , Zugazagoitia Jon , Iglesias-Docampo Lara , Enguita Ana B. , Paz-Ares Luis , Nuñez-Sobrino Juan A. 
Published: July 2016

BACKGROUND: Pemetrexed is an effective antineoplastic agent as monotherapy (second line and maintenance setting) or in platinum-based combination regimes (first-line). Pemetrexed inhibits three key enzymes in the folate metabolic pathway: thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyl transferase (GARFT). As a consequence, pemetrexed interferes with the synthesis of both pyrimidine and purine, thereby effectively inhibiting both DNA and RNA synthesis. The aim of this study was to investigate the impact of the PBMC (peripheral blood mononuclear cells) expression levels of AEG1, BRCA1, REV3like, ant TYMS mRNA in the clinical outcome in NSCLC patients treated with Pemetrexed-based therapy.

MATERIAL AND METHODS: This is a prospective, observational cohort study, of consecutively selected patients. We included patients with non-squamous NSCLC, stage IV, treated with platinum-based chemotherapy plus Pemetrexed. Blood samples from each patient were collected at the beginning of treatment. Quantitative reverse transcription (qRT)-PCR was performed with the use of the TaqMan gene expression assay (Applied Biosystems) according to the manufacturer's instructions. Amplifications were carried out on the Applied Biosystem 7500 RT-PCR system, and relative gene expression values were calculated by the ΔΔCt method (Sequence Detection System 2.0.5). Results from analysis, done in triplicate, are expressed relative to expression levels of GAPDH.

RESULTS: We here present preliminary results of 16 patients included in the study: median age was 63.4 (range 52-82); 12 were males. Histological subtypes were 13 adenocarcinomas, and 3 large cell carcinomas. Pemetrexed was combined with Carboplatin in 9 patients and Cisplatin in 7 patients. Best response obtained was partial response in 7 patients, stable disease in 3 patients, and progression in 5 patients. We found significant differences in the REV3like expression levels between patients with PR&SD and patients with PD (0.69 ± 0.14 vs 0.44 ± 0.07; P = 0.003). In addition there were statistically significant differences in disease free survival (3 ± 0.74 vs 13 ± 1.89, P = 0.035; 12 ± 2.32 vs 3 ± 2.19, P = 0.003, months), and overall survival (10 ± 5.21 vs not reached, P = 0.026; not reached vs 12 ± 2.38, P = 0.007, months) between patients with mRNA levels of REV3like and TYMS under mean value of the cohort and patients with levels over mean value of the our cohort.

CONCLUSIONS: This study supports the value of the PBMC expression profiling of the REV3like and TYMS genes in the prognosis of NSCLC treated with platinum-based chemotherapy plus Pemetrexed.

Citation Format: Maria Teresa Agullo-Ortuño, C.Vanessa Díaz-García, José A. López-Martín, Elena Prieto-García, Santiago Ponce, Jon Zugazagoitia, Lara Iglesias-Docampo, Ana B. Enguita, Luis Paz-Ares, Juan A. Nuñez-Sobrino. Prognostic significance of REV3like and TYMS gene expression in blood samples from non-small cell lung patients treated with platinum-based chemotherapy plus pemetrexed. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2263.