title: Folate Receptor-Positive Circulating Tumor Cell Detected by LT-PCR-Based Method as a Diagnostic Biomarker for Non-Small-Cell Lung Cancer.
abstract: BACKGROUND
  To investigate the diagnostic performance of folate receptor-positive circulating tumor cells in distinguishing non-small-cell lung cancer (NSCLC) from lung benign disease by using a novel ligand-targeted polymerase chain reaction (PCR) detection technique.
  
  
  METHODS
  Circulating tumor cells were enriched from 3-ml peripheral blood by immunomagnetic depletion of leukocytes and then labeled with a conjugate of a tumor-specific ligand folic acid and a synthesized oligonucleotide. After washing off free conjugates, the stripped bound conjugates were analyzed by quantitative PCR.
  
  
  RESULTS
  Seven hundred fifty-six participants (473 patients with NSCLC, 227 patients with lung benign disease, and 56 healthy donors) were randomly assigned to a training set and a test set. The circulating tumor cell (CTC) levels in patients with NSCLC were significant higher than those with lung benign disease (p < 0.001) and healthy donors (p < 0.001). Compared with carcinoembryonic antigen, neuron-specific enolase, and Cyfra21-1, CTCs displayed the highest area under the receiver operating characteristic curve (training set, 0.815; validation set, 0.813) in the diagnosis of NSCLC, with a markedly sensitivity (training set, 72.46%; validation set, 76.37%) and specificity (training set, 88.65%; validation set, 82.39%). The model combining CTCs with carcinoembryonic antigen, neuron-specific enolase, and Cyfra21-1 was more effective for the diagnosis of NSCLC than tumor makers alone (sensitivity and specificity in the training set, 84.21% and 83.91%; validation set, 88.78% and 87.36%, respectively). In addition, the CTC levels were higher in patients with stage III/IV NSCLC compared with those with stage I/II disease.
  
  
  CONCLUSIONS
  Ligand-targeted PCR technique was feasible and reliable for detecting folate receptor-positive CTCs in patients with NSCLC, and CTC levels could be used as a useful biomarker for the diagnosis of NSCLC.
authors.affiliation: Departments of *Medical Oncology and †Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Tongji University, Shanghai, People's Republic of China; and ‡GenoSaber Biotech, Shanghai, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.forename: Guohua
authors.initials: G
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.forename: Qinfang
authors.initials: Q
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Guanghui
authors.initials: G
authors.lastname: Gao
authors.forename: Aiwu
authors.initials: A
authors.lastname: Li
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D001987:Bronchiectasis / Q000097:blood / Q000175:diagnosis; D002272:Carcinoembryonic Antigen / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D004311:Double-Blind Method; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000097:blood* / Q000235:genetics; D006801:Humans; D053539:Keratin-19 / Q000097:blood; D008024:Ligands; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000737:chemistry*; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011014:Pneumonia / Q000097:blood / Q000175:diagnosis; D011030:Pneumothorax / Q000097:blood / Q000175:diagnosis; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D012372:ROC Curve; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D058973:Folate Receptors, GPI-Anchored; D053539:Keratin-19; D008024:Ligands; C102012:antigen CYFRA21.1; D010751:Phosphopyruvate Hydratase