Miao Ti-Wei, Du Long-Yi, Xiao Wei, Mao Bing, Wang Yan, Fu Juan-Juan
Respiratory Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
Research Core Facility, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2021 Mar 9;11:600243. doi: 10.3389/fonc.2021.600243. eCollection 2021.
Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, which is associated with a worse prognosis. Thousands of biomarkers related to the survival of lung cancer have been investigated. However, those which can predict the survival of lung cancer coexisting with COPD are currently lacking. The present study aimed to identify novel gene signatures to predict the survival of patients with lung cancer coexisting COPD. RNA-sequence data of lung cancer and control accompanying with matched clinical information were retrieved from the Cancer Genome Atlas (TCGA). Differently expressed genes (DEGs) associated with lung cancer coexisting COPD were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Univariate and multivariate Cox regression analyses were applied to identify survival-associated DEGs and to construct survival-associated gene signature. Kaplan-Meier survival analysis and calibration plots of the nomogram were performed to test the predictive accuracy of the gene signature. qPCR was performed to validate the genes in the prognostic signature. Sequence data from 70 patients with lung cancer coexisting COPD, 127 with lung cancer alone and 108 control tissues were included for analysis. A total of 2424 DEGs were identified when comparing lung cancer coexisting COPD with controls. The biological process was primarily associated with DNA-binding transcription activator activity, peptidase inhibitor activity, endopeptidase inhibitor activity, et al. KEGG pathways were mainly enriched in neuroactive ligand-receptor interaction, cell cycle, and infection. A survival-associated gene signature consisting of , and was identified and represented as risk score. The high-risk score group had significantly worse survival than the low-risk score group ( < 0.001). Areas under receiver operating characteristic curves were 0.943, 0.773, 0.888 for predicting overall survival at 1-, 3-, and 5-year, respectively. The risk score was an independent predictor of survival, independent of clinical factors. High conformity of the actual survival and the nomogram-predicted probability of survival by applying the risk score. Upregulation of the five genes in patients with lung cancer coexisting COPD were confirmed by qPCR in an independent cohort. Our study constructed and validated a novel prognostic gene signature for predicting survival of patient with lung cancer coexisting COPD, which may contribute to the clinical treatment decisions.
慢性阻塞性肺疾病（COPD）与肺癌常并存，这与更差的预后相关。数千种与肺癌生存相关的生物标志物已被研究。然而，目前缺乏能够预测与COPD并存的肺癌患者生存情况的生物标志物。本研究旨在识别新的基因特征以预测与COPD并存的肺癌患者的生存情况。从癌症基因组图谱（TCGA）中检索肺癌及对照的RNA序列数据以及匹配的临床信息。筛选出与COPD并存的肺癌相关的差异表达基因（DEG）。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析。应用单变量和多变量Cox回归分析来识别与生存相关的DEG并构建与生存相关的基因特征。进行Kaplan-Meier生存分析和列线图的校准图以检验基因特征的预测准确性。进行qPCR以验证预后特征中的基因。纳入70例与COPD并存的肺癌患者、127例单纯肺癌患者和108例对照组织的序列数据进行分析。将与COPD并存的肺癌与对照进行比较时，共鉴定出2424个DEG。生物学过程主要与DNA结合转录激活因子活性、肽酶抑制剂活性、内肽酶抑制剂活性等相关。KEGG通路主要富集于神经活性配体-受体相互作用、细胞周期和感染。鉴定出一个由[具体基因名称未给出]组成的与生存相关的基因特征，并表示为风险评分。高风险评分组的生存情况明显比低风险评分组差（P<0.001）。预测1年、3年和5年总生存的受试者工作特征曲线下面积分别为0.943、0.773和0.888。风险评分是生存的独立预测因子，独立于临床因素。应用风险评分时，实际生存与列线图预测的生存概率高度一致。在一个独立队列中，通过qPCR证实了与COPD并存的肺癌患者中这五个基因的上调。我们的研究构建并验证了一种新的预后基因特征，用于预测与COPD并存的肺癌患者的生存情况，这可能有助于临床治疗决策。
