Shang Jun, Song Qian, Yang Zuyi, Li Dongyao, Chen Wenjie, Luo Lei, Wang Yongkun, Yang Jingcheng, Li Shikang
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, P. R. China.
Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Oncotarget. 2017 Aug 2;8(50):87292-87306. doi: 10.18632/oncotarget.19823. eCollection 2017 Oct 20.
As the most common histologic subtype of lung cancer, lung adenocarcinoma (LUAD) contributes to a majority of cancer-related deaths worldwide annually. In order to find specific biomarkers of LUAD that are able to distinguish LUAD from other types of cancer so as to improve the early diagnostic and prognostic power in LUAD, we analyzed 10098 tumor tissue samples across 27 TCGA cancer types and identified 112 specific expressed genes in LUAD. Meantime, 8240 LUAD dysregulated genes in tumor and normal samples were identified. Combining with the results of specific expressed genes and dysregulated genes in LUAD, we found there were 70 specific dysregulated genes in LUAD (LUAD-SDGs). Then ROC curve revealed six LUAD-SDGs that may be of strong diagnostic value to predict the existence of cancer (area under curve[AUC] > 95%). Kaplan-Meier survival analysis was performed to identify 6 LUAD-SDGs associated with patients' prognosis (P-values < 0.001). Multivariate Cox proportional hazards regression was employed to demonstrate that the six LUAD-SDGs were independent prognostic factors. Then, we used the six overall survival (OS)-related LUAD-SDGs constructing a six-gene signature. Multivariate Cox regression analysis suggested that the six-gene signature was an independent prognostic factor of other clinical variables (hazard ratio [HR] = 1.5098, 95%CI = 1.2996-1.7538, P < 0.0001). Based on our findings, we first presented the LUAD-SDGs for LUAD diagnosis and prognosis. Our results may provide efficient biomarkers to clinical diagnostic and prognostic evaluation in LUAD.
作为肺癌最常见的组织学亚型,肺腺癌(LUAD)每年在全球导致大多数癌症相关死亡。为了找到能够将LUAD与其他类型癌症区分开来的LUAD特异性生物标志物,以提高LUAD的早期诊断和预后能力,我们分析了27种TCGA癌症类型的10098个肿瘤组织样本,并在LUAD中鉴定出112个特异性表达基因。同时,在肿瘤和正常样本中鉴定出8240个LUAD失调基因。结合LUAD中特异性表达基因和失调基因的结果,我们发现LUAD中有70个特异性失调基因(LUAD-SDGs)。然后ROC曲线显示6个LUAD-SDGs对预测癌症的存在可能具有很强的诊断价值(曲线下面积[AUC]>95%)。进行Kaplan-Meier生存分析以鉴定与患者预后相关的6个LUAD-SDGs(P值<0.001)。采用多变量Cox比例风险回归证明这6个LUAD-SDGs是独立的预后因素。然后,我们使用6个与总生存(OS)相关的LUAD-SDGs构建了一个六基因特征。多变量Cox回归分析表明,该六基因特征是其他临床变量的独立预后因素(风险比[HR]=1.5098,95%CI=1.2996-1.7538,P<0.0001)。基于我们的发现,我们首次提出了用于LUAD诊断和预后的LUAD-SDGs。我们的结果可能为LUAD的临床诊断和预后评估提供有效的生物标志物。