title: A panel of protein markers for the early detection of lung cancer with bronchial brushing specimens.
abstract: BACKGROUND
  To date, no robust biomarkers have been available in clinical practice that can provide an early diagnostic evaluation of lung cancer. The objective of this study was to identify potential biomarkers for the early detection of lung cancer using bronchial brushing specimens.
  
  
  METHODS
  Immunocytochemistry was used to investigate the expression of 35 proteins in 880 bronchial brushing specimens from both outpatients and inpatients who had either lung cancer or benign lung lesions. An optimal panel was identified that had high sensitivity and considerable specificity for detecting lung cancer. Associations between protein expression and clinicopathologic parameters were assessed.
  
  
  RESULTS
  Tumor protein 53 (TP53), TP63, Ki67, epidermal growth factor receptor (EGFR), minichromosome maintenance complex component 6 (MCM6), MCM7, uncharacterized proteins KIAA1522 and KIAA0317, and ubiquitin-protein ligase UHR1 (ICBP90) frequently presented high expression in bronchial brushing specimens from patients who had lung cancer compared with patients who had benign lung lesions. A 6-protein panel consisting of TP53, Ki67, MCM6, MCM7, KIAA1522, and KIAA0317 was identified as the best combination, with sensitivity of 81.1% (309 of 381 specimens) for detecting nonsmall cell lung cancer (NSCLC) and 86.8% (145 of 167 specimens) for detecting small cell lung cancer (SCLC) (specificity, 83.3%; 65 of 78 specimens). The combination of cytology and the protein panel significantly improved the sensitivity of bronchial brushing examination for detecting lung cancer (P<.00001), which increased from 49.1% to 81% in early stage NSCLC (stage I and II). In combined analyses, the protein panel was positively associated with patient sex (P=.00033), tumor type (P<.00001), tumor location (P<.00001), and lymph node metastasis (P=.028).
  
  
  CONCLUSIONS
  The 6-protein panel is a potential biomarker for the early detection of lung cancer in bronchial brushings.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yi-Zhen
authors.initials: YZ
authors.lastname: Liu
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Jiang
authors.forename: Bo-Shi
authors.initials: BS
authors.lastname: Wang
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Hao
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.forename: Tong-Tong
authors.initials: TT
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Cao
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001980:Bronchi / Q000473:pathology; D001999:Bronchoscopy; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism; D003581:Cytodiagnosis / Q000379:methods; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000378:metabolism; D013048:Specimen Handling / Q000379:methods; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins
keywords: biomarker; bronchial brushings; nonsmall cell lung cancer; protein panel; small cell lung cancer