A Lafuente-Sanchis1, Á Zúñiga2, J M Galbis3, A Cremades4, M Estors3, N J Martínez-Hernández3, J Carretero5. 1. Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain. alafuente@hospital-ribera.com. 2. Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain. 3. Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain. 4. Servicio de Anatomía Patológica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain. 5. Departament de Fisiologia, Facultat de Farmàcia, Universitat de València, Avda. Vicent Andrés Estellés, s/n, 46100, Burjassot, Valencia, Spain.
Abstract
INTRODUCTION: Nowadays, 40 % of early-stage NSCLC patients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLC patients, in early-stage NSCLC patients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLC patients at stage I. PATIENTS AND METHODS: ERCC1, RRM1, BRCA1 and SETDB1 expression at mRNA level was analyzed by real-time quantitative RT-PCR in fresh-frozen tumor and normal adjacent lung tissue samples from 64 stage I NSCLC patients. Later, significant association between gene expression levels, clinicopathological characteristics and patient's disease-free survival was assessed. RESULTS: We did not find any statistically significant correlation between gene expression and gender, age, histological type or smoking status. Univariate followed by multivariate Cox analysis showed that higher levels of BRCA1 and SETDB1 expression were significantly associated with shorter disease-free survival in stage I NSCLC patients. CONCLUSION: Our study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLC patients. By contrast, BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence in early-stage NSCLC patients.
INTRODUCTION: Nowadays, 40 % of early-stage NSCLCpatients relapse in the 2 years following resection, suggesting a mis-staging in this group of patients who are not receiving adjuvant chemotherapy. Although different biomarkers, such as ERCC1, RRM1 and BRCA1 have been found to present prognostic value in advanced NSCLCpatients, in early-stage NSCLCpatients its relevance remains unclear. Moreover, SETDB1 has been recently proposed as a bona fide oncogene in lung tumourigenesis and related with metastasis. The aim of the present study was to analyze the prognostic value of ERCC1, RRM1, BRCA1 and SETDB1 expression levels in NSCLCpatients at stage I. PATIENTS AND METHODS: ERCC1, RRM1, BRCA1 and SETDB1 expression at mRNA level was analyzed by real-time quantitative RT-PCR in fresh-frozen tumor and normal adjacent lung tissue samples from 64 stage I NSCLCpatients. Later, significant association between gene expression levels, clinicopathological characteristics and patient's disease-free survival was assessed. RESULTS: We did not find any statistically significant correlation between gene expression and gender, age, histological type or smoking status. Univariate followed by multivariate Cox analysis showed that higher levels of BRCA1 and SETDB1 expression were significantly associated with shorter disease-free survival in stage I NSCLCpatients. CONCLUSION: Our study finds that ERCC1 and RRM1 are not independent prognostic factors of recurrence in stage I NSCLCpatients. By contrast, BRCA1 and SETDB1 stand out as the most significant prognostic markers in this group of patients, appearing as promising tools to predict tumor recurrence in early-stage NSCLCpatients.
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