title: Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.
abstract: BACKGROUND
  Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis.
  
  
  METHODS
  Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE.
  
  
  RESULTS
  The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93.
  
  
  CONCLUSIONS
  CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Zeng
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wan
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China. shen_yongchun@126.com.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China. shen_yongchun@126.com.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.|Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu, 610041, China.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000473:pathology; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018395:CA-19-9 Antigen / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D008175:Lung Neoplasms / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D012372:ROC Curve
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C102012:antigen CYFRA21.1
keywords: Diagnosis; Lung adenocarcinoma; Malignant pleural effusion; Meta-analysis; Tumor marker