Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.
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.
Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.|Shanghai Respiratory Research Institute, Shanghai, China.
Hai-Xing
HX
Zhu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Lin
L
Shi
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Shanghai Respiratory Research Institute, Shanghai, China.
Yong
Y
Zhang
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Yi-Chun
YC
Zhu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Shanghai Respiratory Research Institute, Shanghai, China.
Chun-Xue
CX
Bai
Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China.|Fudan University Center for Clinical Bioinformatics, Shanghai, China.
Xiang-Dong
XD
Wang
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. zhou.jiebai@zs-hospital.sh.cn.|Shanghai Respiratory Research Institute, Shanghai, China. zhou.jiebai@zs-hospital.sh.cn.
Jie-Bai
JB
Zhou
D000072283:A549 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064326:MEF2 Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000235:genetics
D008070:Lipopolysaccharides; D064326:MEF2 Transcription Factors; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases
Biomarker; Clinical bioinformatics; Inflammation; Lung cancer; Myocyte enhancer factor 2D