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J. Cancer Mol. 3: 107-112, 2007

[Research Paper]

Elevation of Serum HSP90alpha Correlated with the Clinical Stage of Non-Small Cell Lung Cancer

Anjian Xu, Tian Tian, Jia Hao, Jifu Liu, Zhao Zhang, Juanting Hao, Shanshan Wu, Lingyun Huang, Xueyuan Xiao, and Dacheng He

Key laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, Beijing, China [A. Xu, T. Tian, J. Hao, Z. Zhang, J. Hao, L. Huang, X. Xiao, D. He]; Department of Thoracic Surgery, General Hospital of Beijing Unit, PLA, Beijing, China [J. Liu, S. Wu]

Abstract:

   AIM: The heat shock protein HSP90alpha, reportedly expressing in cytoplasm, had been recently detected in serum-free cultured medium (CM) from fibrosarcoma cells and breast adenocarcinoma cells.  The present study was designed to investigate whether HSP90alpha could be found in the CM of lung cancer cell lines, and is a sensitive and specific serum biomarker for the diagnosis and progression of lung cancer.

METHODS: In the present study, different secretomic analyses on the two human lung adenocarcinoma cell lines CL1-0 and CL1-5 with low and high metastatic potential, respectively, were performed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.  The candidate biomarker was confirmed by immunoprecipitation and Western blot, and was further analyzed in 224 serum samples including 141 lung cancer, 37 benign pulmonary diseases, as well as 46 healthy individuals using ELISA assay.

RESULTS: Six biomarkers were identified, of which HSP90alpha was significantly up-regulated in the CM of CL1-5 cells.  It was found that the levels of HSP90alpha were specifically elevated in the sera of non-small cell lung cancer compared with other groups and were progressively increased with the clinical stage.  At the cut-off point 0.535 on the Receiver Operating Characteristic curve, HSP90alpha could comparatively discriminate lung cancer from benign lung disease and healthy control groups with sensitivity 0.817, specificity 0.919 and total accuracy 80.14%. 

CONCLUSION: HSP90alpha may be a potential useful serum biomarker to discriminate lung cancer from the benign lung diseases and healthy individuals and the stage of non-small cell lung cancer.

(Keywords: HSP90alpha; CL1-0; CL1-5; secretome; metastasis)______________________________________________________________________________________________________________

Received 7/18/07; Revised 8/7/07; Accepted 8/8/07.

1Correspondence: Dr. Xueyuan Xiao or Dr. Dacheng He, Key Laboratory of Cell Proliferation and Regulation of Ministry of Education, Beijing Normal University, 19th Xinjiekouwai Street 100875, Beijing, China. Fax: 86-10-58809729. E-mail: xuanjian1981@yahoo.com.cn

2Abbreviations: NSCLC, non-small cell lung cancer; AD, adenocarcinoma; CM, cultured medium; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; PGK1, phosphoglycerate kinase 1; ENOA, a-enolase; TPIS, triosephosphate isomerase; G6PI, glucose-6-phosphate isomerase; LDH-B, L-lactate dehydrogenase B chain; TFA, trifluoroacetic acid; ROC, Receiver Operating Characteristic; SCLC, small cell lung carcinoma.

 

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