Abstract：
High dose intravenous vitamin C (IVC) has been proposed as a pro-oxidant anticancer agent. However, there is a lack of biomarkers that are specific for this treatment. Here, we explored profiles of gene expression responding to IVC treatment in non-small cell lung cancer (NSCLC) cells as an effort for potential biomarker discovery. Genome-wide RNA-seq was performed in human NSCLC cell lines treated with pharmacological concentrations of vitamin C(VitC) for differential expression of genes. The identified genes were analyzed for correlations with patient prognosis using data from the Kaplan-Meier Plotter and the Human Protein Atlas databases. Further, tumor samples from a retrospective study of 153 NSCLC patients were analyzed with immunohistochemistry for expression of targeted genes, and patient prognosis was correlated to these genes. Two genes, namely SERPINE1 and SERPINB7 were found to be downregulated in NSCLC cells following VitC treatment. Combined patient data from the cohort analysis and online databases revealed that these 2 genes presented an unfavorable prognostic prediction of overall survival (OS) in NSCLC patients receiving standard of care. However, high expression level of these 2 genes were associated with prolonged OS in NSCLC patients receiving IVC in addition to standard of care. These data revealed that SERPINE1 and SERPINB7 have the potential to serve as predictive factors indicating favorable responses to IVC treatment in patients with NSCLC. Further validations are warranted.
摘要：
已提出高剂量静脉内维生素C（IVC）作为促氧化抗癌剂。然而,缺乏对这种治疗具有特异性的生物标志物.这里,我们探索了在非小细胞肺癌(NSCLC)细胞中响应IVC治疗的基因表达谱,作为潜在生物标志物发现的一项努力.在用药理学浓度的维生素C(VitC)处理的人NSCLC细胞系中进行全基因组RNA-seq以用于基因的差异表达。使用来自Kaplan-Meier绘图仪和人类蛋白质图谱数据库的数据,分析鉴定的基因与患者预后的相关性。Further,对来自153例NSCLC患者的回顾性研究的肿瘤样本进行了免疫组织化学分析，以确定靶基因的表达。患者预后与这些基因相关。两个基因,即在VitC处理后,发现在NSCLC细胞中SERPINE1和SERPINB7下调。来自队列分析和在线数据库的合并患者数据显示，这2个基因在接受标准治疗的NSCLC患者中呈现总体生存（OS）的不利预后预测。然而,在接受IVC和标准治疗的NSCLC患者中,这2种基因的高表达水平与OS延长相关.这些数据显示，SERPINE1和SERPINB7有可能作为预测因子，表明NSCLC患者对IVC治疗有良好反应。需要进一步的验证。
