Zhu Hai-Xing, Shi Lin, Zhang Yong, Zhu Yi-Chun, Bai Chun-Xue, Wang Xiang-Dong, Zhou Jie-Bai
Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Shanghai Respiratory Research Institute, Shanghai, China.
J Transl Med. 2017 Mar 24;15(1):65. doi: 10.1186/s12967-017-1168-x.
Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases.
We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis.
Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement.
Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.
肺癌是全球癌症相关发病和死亡的主要原因。患有慢性呼吸道疾病（如慢性阻塞性肺疾病，COPD）的患者患肺癌的风险更高。慢性炎症可能在这些患者的肺癌发生过程中起重要作用。本研究旨在确定预测慢性呼吸道疾病患者肺癌风险的候选生物标志物。
我们应用临床生物信息学工具分析不同的基因谱数据集，特别关注在慢性炎症 - 肺癌转变过程中筛选潜在的生物标志物。然后我们采用基于脂多糖刺激的A549细胞的体外模型，通过RNA测序、定量实时聚合酶链反应和蛋白质印迹分析来验证该生物标志物。
对来自基因表达综合在线数据库的16个已登记GSE数据集的生物信息学分析表明，在合并非小细胞肺癌（NSCLC）的COPD患者中，肌细胞增强因子2D（MEF2D）水平显著升高。炎症刺激增加了NSCLC细胞系A549中MEF2D的表达，这与炎症的严重程度相关。细胞外信号调节蛋白激酶抑制可逆转炎症激活的A549中MEF2D的上调。MEF2D在NSCLC细胞的生物学行为中起关键作用，包括增殖、分化和迁移。
炎症状态导致MEF2D表达增加，这可能通过影响癌症微环境和细胞生物学行为进一步促进肺癌的发展。MEF2D可能是慢性炎症 - 肺癌转变过程中的潜在生物标志物，可预测慢性呼吸道疾病患者的肺癌风险。
