PMID- 25045014 OWN - NLM STAT- MEDLINE DCOM- 20150126 LR - 20151119 IS - 1934-6638 (Electronic) IS - 1934-662X (Linking) VI - 122 IP - 11 DP - 2014 Nov TI - A panel of protein markers for the early detection of lung cancer with bronchial brushing specimens. PG - 833-41 LID - 10.1002/cncy.21461 [doi] AB - 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. CI - (c) 2014 American Cancer Society. FAU - Liu, Yi-Zhen AU - Liu YZ AD - State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. FAU - Jiang, Yan-Yi AU - Jiang YY FAU - Wang, Bo-Shi AU - Wang BS FAU - Hao, Jia-Jie AU - Hao JJ FAU - Shang, Li AU - Shang L FAU - Zhang, Tong-Tong AU - Zhang TT FAU - Cao, Jian AU - Cao J FAU - Xu, Xin AU - Xu X FAU - Zhan, Qi-Min AU - Zhan QM FAU - Wang, Ming-Rong AU - Wang MR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140709 PL - United States TA - Cancer Cytopathol JT - Cancer cytopathology JID - 101499453 RN - 0 (Biomarkers, Tumor) RN - 0 (Proto-Oncogene Proteins) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*biosynthesis MH - Bronchi/pathology MH - Bronchoscopy MH - Carcinoma, Non-Small-Cell Lung/diagnosis/metabolism MH - Cytodiagnosis/methods MH - Diagnosis, Differential MH - Early Diagnosis MH - Female MH - Humans MH - Immunohistochemistry MH - Lung Neoplasms/*diagnosis/*metabolism MH - Male MH - Middle Aged MH - Proto-Oncogene Proteins/*biosynthesis MH - Reproducibility of Results MH - Sensitivity and Specificity MH - Small Cell Lung Carcinoma/diagnosis/metabolism MH - Specimen Handling/methods MH - Young Adult OTO - NOTNLM OT - biomarker OT - bronchial brushings OT - nonsmall cell lung cancer OT - protein panel OT - small cell lung cancer EDAT- 2014/07/22 06:00 MHDA- 2015/01/27 06:00 CRDT- 2014/07/22 06:00 PHST- 2014/04/24 00:00 [received] PHST- 2014/05/29 00:00 [revised] PHST- 2014/06/10 00:00 [accepted] PHST- 2014/07/22 06:00 [entrez] PHST- 2014/07/22 06:00 [pubmed] PHST- 2015/01/27 06:00 [medline] AID - 10.1002/cncy.21461 [doi] PST - ppublish SO - Cancer Cytopathol. 2014 Nov;122(11):833-41. doi: 10.1002/cncy.21461. Epub 2014 Jul 9.