Institut universitaire de cardiologie et de pneumologie de Québec, Quebec, Canada.
Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec, Canada.
PLoS One. 2018 Nov 20;13(11):e0207513. doi: 10.1371/journal.pone.0207513. eCollection 2018.
Prognostic biomarkers are needed in clinical setting to predict outcome after resection for early-stage lung adenocarcinoma. The goal of this study is to validate tumor-based single-gene expression biomarkers with demonstrated prognostic value in order to move them along the clinical translation pipeline.
Prognostic genes were selected from the literature and the best candidates measured by quantitative real-time polymerase chain reaction (qPCR) in tumors of 233 patients with stage I adenocarcinoma. Significant prognostic genes were then validated in an independent set of 210 patients matching the first set in terms of histology, stage, and clinical data.
Eleven genes with demonstrated prognostic value were selected from the literature. Complementary analyses in public databases and our own microarray dataset led to the investigation of six genes associated with good (BTG2, SELENBP1 and NFIB) or poor outcome (RRM1, EZH2 and FOXM1). In the first set of patients, EZH2 and RRM1 were significantly associated with better survival on top of age, sex and pathological stage (EZH2 p = 3.2e-02, RRM1 p = 5.9e-04). The prognostic values of EZH2 and RRM1 were not replicated in the second set of patients. A trend was observed for both genes in the joint analyses (n = 443) with higher expression associated with worse outcome.
Adenocarcinoma-specific mRNA expression levels of EZH2 and RRM1 are associated with poor post-surgical survival in the first set of patients, but not replicated in a clinically and pathologically matched independent validation set. This study highlights challenges associated with clinical translation of prognostic biomarkers.
在临床环境中需要预后生物标志物来预测早期肺腺癌切除术后的结果。本研究的目的是验证具有明确预后价值的基于肿瘤的单基因表达生物标志物，以便将其推进临床转化管道。
从文献中选择预后基因，并通过定量实时聚合酶链反应 (qPCR) 在 233 例 I 期腺癌患者的肿瘤中测量最佳候选基因。然后在与第一组在组织学、分期和临床数据方面相匹配的 210 例患者的独立组中验证有意义的预后基因。
从文献中选择了 11 个具有明确预后价值的基因。在公共数据库和我们自己的微阵列数据集的补充分析中，研究了与良好（BTG2、SELENBP1 和 NFIB）或不良结果相关的六个基因（RRM1、EZH2 和 FOXM1）。在第一组患者中，EZH2 和 RRM1 在年龄、性别和病理分期之上与更好的生存相关（EZH2 p = 3.2e-02，RRM1 p = 5.9e-04）。在第二组患者中，EZH2 和 RRM1 的预后价值未得到复制。在联合分析（n = 443）中观察到这两个基因均呈趋势，表达较高与结局较差相关。
EZH2 和 RRM1 在腺癌特异性 mRNA 表达水平与第一组患者手术后生存不良相关，但在临床和病理匹配的独立验证组中未复制。本研究强调了与预后生物标志物临床转化相关的挑战。
