Lafuente-Sanchis A, Zúñiga Á, Galbis J M, Cremades A, Estors M, Martínez-Hernández N J, Carretero J
Servicio de Genética-Biología Molecular, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
Servicio de Cirugía Torácica, Hospital Universitario de la Ribera, ctra. Corbera, km.1, 46600, Alzira, Spain.
Clin Transl Oncol. 2016 Aug;18(8):798-804. doi: 10.1007/s12094-015-1440-6. Epub 2015 Nov 5.
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.
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.
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.
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.
如今，40%的早期非小细胞肺癌（NSCLC）患者在切除术后2年内复发，这表明在未接受辅助化疗的这组患者中存在分期错误。尽管已发现不同的生物标志物，如ERCC1、RRM1和BRCA1在晚期NSCLC患者中具有预后价值，但在早期NSCLC患者中其相关性仍不明确。此外，SETDB1最近被认为是肺肿瘤发生中的一种真正致癌基因，且与转移相关。本研究的目的是分析ERCC1、RRM1、BRCA1和SETDB1表达水平在I期NSCLC患者中的预后价值。
通过实时定量逆转录聚合酶链反应（RT-PCR）分析了64例I期NSCLC患者新鲜冷冻肿瘤及癌旁正常肺组织样本中ERCC1、RRM1、BRCA1和SETDB1的mRNA水平表达。随后，评估了基因表达水平、临床病理特征与患者无病生存期之间的显著相关性。
我们未发现基因表达与性别、年龄、组织学类型或吸烟状态之间存在任何统计学显著相关性。单因素分析后进行多因素Cox分析显示，BRCA1和SETDB1表达水平较高与I期NSCLC患者较短的无病生存期显著相关。
我们的研究发现，ERCC1和RRM1不是I期NSCLC患者复发的独立预后因素。相比之下，BRCA1和SETDB1是这组患者中最显著的预后标志物，有望成为预测早期NSCLC患者肿瘤复发的工具。
