Zhou Shijie, Wang Ping, Su Xiaolan, Chen Jingxia, Chen Hongfen, Yang Hanbing, Fang Aiping, Xie Linshen, Yao Yuqin, Yang Jinliang
Research Center for Public Health and Preventive Medicine, West China School of Public Health/No.4 West China Teaching Hospital, Sichuan University, Chengdu, China.
Cancer Center, West China Medical School, West China Hospital, Sichuan University, Chengdu, China.
PLoS One. 2017 Oct 31;12(10):e0187356. doi: 10.1371/journal.pone.0187356. eCollection 2017.
Different subtypes of non-small cell lung cancer (NSCLC) have distinct sites of origin, histologies, genetic and epigenetic changes. In this study, we explored the mechanisms of ECT2 dysregulation and compared its prognostic value in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, we also investigated the enrichment of ECT2 co-expressed genes in KEGG pathways in LUAD and LUSC. Bioinformatic analysis was performed based on data from the Cancer Genome Atlas (TCGA)-LUAD and TCGA-LUSC. Results showed that ECT2 expression was significantly upregulated in both LUAD and LUSC compared with normal lung tissues. ECT2 expression was considerably higher in LUSC than in LUAD. The level of ECT2 DNA methylation was significantly lower in LUSC than in LUAD. ECT2 mutation was observed in 5% of LUAD and in 51% of LUSC cases. Amplification was the predominant alteration. LUAD patients with ECT2 amplification had significantly worse disease-free survival (p = 0.022). High ECT2 expression was associated with unfavorable overall survival (OS) (p<0.0001) and recurrence-free survival (RFS) (p = 0.001) in LUAD patients. Nevertheless, these associations were not observed in patients with LUSC. The following univariate and multivariate analysis showed that the high ECT2 expression was an independent prognostic factor for poor OS (HR: 2.039, 95%CI: 1.457-2.852, p<0.001) and RFS (HR: 1.715, 95%CI: 1.210-2.432, p = 0.002) in LUAD patients, but not in LUSC patients. Among 518 genes co-expressed with ECT2 in LUAD and 386 genes co-expressed with ECT2 in LUSC, there were only 98 genes in the overlapping cluster. Some of the genes related KEGG pathways in LUAD were not observed in LUSC. These differences might help to explain the different prognostic value of ECT2 in LUAD and LUSC, which are also worthy of further studies.
非小细胞肺癌（NSCLC）的不同亚型具有不同的起源部位、组织学特征、基因和表观遗传学变化。在本研究中，我们探讨了ECT2失调的机制，并比较了其在肺腺癌（LUAD）和肺鳞状细胞癌（LUSC）中的预后价值。此外，我们还研究了LUAD和LUSC中ECT2共表达基因在KEGG通路中的富集情况。基于来自癌症基因组图谱（TCGA）-LUAD和TCGA-LUSC的数据进行了生物信息学分析。结果显示，与正常肺组织相比，ECT2在LUAD和LUSC中的表达均显著上调。ECT2在LUSC中的表达明显高于LUAD。LUSC中ECT2的DNA甲基化水平显著低于LUAD。在5%的LUAD病例和51%的LUSC病例中观察到ECT2突变。扩增是主要的改变。ECT2扩增的LUAD患者无病生存期显著更差（p = 0.022）。ECT2高表达与LUAD患者的总生存期（OS）不良（p<0.0001）和无复发生存期（RFS）不良（p = 0.001）相关。然而，在LUSC患者中未观察到这些关联。随后的单因素和多因素分析表明，ECT2高表达是LUAD患者OS不良（HR：2.039，95%CI：1.457 - 2.852，p<0.001）和RFS不良（HR：1.715，95%CI：1.210 - 2.432，p = 0.002）的独立预后因素，但在LUSC患者中并非如此。在LUAD中与ECT2共表达的518个基因和LUSC中与ECT2共表达的386个基因中，重叠簇中只有98个基因。LUAD中一些与KEGG通路相关的基因在LUSC中未观察到。这些差异可能有助于解释ECT2在LUAD和LUSC中不同的预后价值，这也值得进一步研究。
