Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
Oncology Department, Nicosia General Hospital, Nicosia, Cyprus.
Anticancer Res. 2020 Feb;40(2):901-913. doi: 10.21873/anticanres.14023.
BACKGROUND/AIM: Tumoural transcriptional levels of RRM1, RRM2, CDA, dCK and hENT1 genes are potential biomarkers for gemcitabine's efficacy in non-small cell lung cancer (NSCLC).
We retrospectively analysed each gene's relative mRNA expression by quantitative, real-time polymerase chain reaction in microdissected, formalin-fixed, paraffin-embedded primary-tumour specimens from 219 chemonaïve patients with advanced-stage NSCLC, treated with gemcitabine-based regimens within clinical trials. The five genes' transcriptional patterns were integrated into an ordinal, five-level gemcitabine-susceptibility classifier (5L-GSC).
Treatment efficacy increased progressively across the five susceptibility levels, with the very-high chemosensitivity cases obtaining the most clinical benefit. 5L-GSC emerged as an independent prognosticator for overall response and disease control rates, time to progression and overall survival at p-values of 0.03, 0.004, <0.001 and <0.001, respectively, with results remaining significant after bootstrapping. Penalised, optimally-scaled, categorical-regression modelling of overall response identified 5L-GSC as the most stable predictor.
The proposed composite biomarker is promising for customising front-line chemotherapy in NSCLC.
背景/目的：RRM1、RRM2、CDA、dCK 和 hENT1 基因的肿瘤转录水平是吉西他滨治疗非小细胞肺癌（NSCLC）疗效的潜在生物标志物。
我们通过定量实时聚合酶链反应，对 219 例未经化疗的晚期 NSCLC 患者的微切割、福尔马林固定、石蜡包埋的原发性肿瘤标本中的每个基因的相对 mRNA 表达进行了回顾性分析，这些患者接受了临床试验中的吉西他滨为基础的方案治疗。将这 5 个基因的转录模式整合到一个有序的、5 级吉西他滨敏感性分类器（5L-GSC）中。
治疗效果随着五个敏感性水平的提高而逐渐提高，高化疗敏感性病例获得了最大的临床获益。5L-GSC 作为总反应率和疾病控制率、无进展时间和总生存率的独立预后因素，p 值分别为 0.03、0.004、<0.001 和<0.001，Bootstrapping 后结果仍然具有显著性。整体反应的最优尺度、分类回归模型的惩罚性分析确定 5L-GSC 是最稳定的预测因子。
所提出的复合生物标志物有望用于 NSCLC 一线化疗的个体化定制。
