Abstract
Currently, no satisfactory biomarkers are available to screen for small‐cell lung cancer (SCLC). We applied a surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry (SELDI‐TOF MS) ProteinChip system to detect 150 serum samples (including 54 SCLC patients, 24 non‐small cell lung cancer [NSCLC] patients, 32 pneumonia patients, and 40 healthy individuals). The spectra data were analyzed by support vector machine (SVM) and potential biomarkers were chosen for the system training and used to construct diagnostic model. Pattern 1, constructed of four protein peaks with mass/charge (m/z) of 4,293 Da, 4,612 Da, 6,455 Da, and 7,582 Da, separated SCLC patients from the healthy individuals with a sensitivity of 88.9% and a specificity of 85.7%. This pattern performed significantly better than the current marker, neuron‐specific enolase (NSE) (P<0.05). Pattern 2, constructed of protein peaks with mass/charge (m/z) of 2,764 Da and 1,7368 Da, separated SCLC from pneumonia with a sensitivity of 88.9% and a specificity of 91.7%. Pattern 3, constructed of another three protein peaks with m/z of 3,912 Da, 7,562 Da, and 13,777 Da, separated SCLC from NSCLC. The sensitivity and specificity were 83.3% and 75.0%, respectively. These results suggested that SELDI‐TOF MS combined with support vector machine yields significantly higher sensitivity and specificity for the detection of serum protein of SCLC. J. Clin. Lab. Anal. 22:131–137, 2008. © 2008 Wiley‐Liss, Inc.
Keywords: biomarker, diagnosis, proteomics, lung cancer, SELDI‐TOF MS
Abbreviations | |
---|---|
CV | coefficient of variance |
m/z | mass/charge |
H | hydrophobic |
N‐SCLC | non‐small‐cell lung cancer |
NSE | neuron‐specific enolase |
QC | quality control |
ROC | receiver operator characteristic curve |
SCLC | small cell lung cancer |
SELDI‐TOF MS | surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry |
SVM | support vector machine |
UDWT | undecimated discrete wavelet transform. |
REFERENCES
- 1. Manegold C, Thatcher N. Survival improvement in thoracic cancer: progress from the last decade and beyond. Lung Cancer 2007;57:S3–S5. [DOI] [PubMed] [Google Scholar]
- 2. Granetzny A, Boseila A, Wagner W, et al. Surgery in the tri‐modality treatment of small cell lung cancer: stage‐dependent survival. Eur J Cardiothorac Surg 2006;30:212–216. [DOI] [PubMed] [Google Scholar]
- 3. Bharti A, Ma PC, Salgia R. Biomarker discovery in lung cancer‐promises and challenges of clinical proteomics. Mass Spectrom Rev 2007;26:451–466. [DOI] [PubMed] [Google Scholar]
- 4. Arita T, Kuramitsu T, Kawamura M, et al. Bronchogenic carcinoma: incidence of metastasis to normal sized lymph nodes. Thorax 1995;50:1257–1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Hatzakis KD, Froudarakis ME, Bouros D, Tzanakis N, Karkavitsas N, Siafakas NM. Prognostic value of serum tumor markers in patients with lung cancer. Respiration 2002;69:25–29. [DOI] [PubMed] [Google Scholar]
- 6. Lee JH, Chang JH. Diagnostic utility of serum and pleural fluid carcinoembryonic antigen, neuron specific enolase and cytokeratin 19 fragments in patients with effusion from primary lung cancer. Chest 2005;128:2298–2303. [DOI] [PubMed] [Google Scholar]
- 7. Pujol JL, Quantin X, Jacot W, Boher JM, Grenier J, Lamy PJ. Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer. Lung Cancer 2003;39:131–138. [DOI] [PubMed] [Google Scholar]
- 8. Titulaer MK, Siccama I, Dekker LJ, et al. A database application for pre‐processing, storage and comparison of mass spectra derived from patients and controls. BMC Bioinformatics 2006;7:403. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Jemal A, Murray T, Samuels A, Chafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5–6. [DOI] [PubMed] [Google Scholar]
- 10. Engwegen JY, Gast MC, Schellens JH, Beijnen JH. Clinical proteomics: searching for better tumour markers with SELDI‐TOF mass spectrometry. Trends Pharmacol Sci 2006;27:251–259. [DOI] [PubMed] [Google Scholar]
- 11. Yu Y, Chen S, Wang LS, et al. Prediction of pancreatic cancer by serum biomarkers using surface‐enhanced laser desorption/ionization‐based decision tree classification. Oncology 2005;68:79–86. [DOI] [PubMed] [Google Scholar]
- 12. Petricoin EF, Liotta LA. SELDI‐TOF‐based serum proteomic pattern diagnostics for early detection of cancer. Curr Opin Biotechnol 2004;15:24–30. [DOI] [PubMed] [Google Scholar]
- 13. Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002;359:572–577. [DOI] [PubMed] [Google Scholar]
- 14. Li J, Zhang Z, Rosenzweig J, Wang YY, Chan DW. Proteomics and bioinformatics approaches for identification of serum biomarkers to detect breast cancer. Clin Chem 2002;48:1296–1304. [PubMed] [Google Scholar]
- 15. Vlahou A, Laronga C, Wilson L, et al. A novel approach toward development of a rapid blood test for breast cancer. Clin Breast Cancer 2003;4:203–209. [DOI] [PubMed] [Google Scholar]
- 16. Koopmann J, Zhang Z, White N, et al. Serum diagnosis of pancreatic adenocarcinoma using surface‐enhanced laser desorption and ionization mass spectrometry. Clin Cancer Res 2004;10:860–868. [DOI] [PubMed] [Google Scholar]
- 17. Chen YD, Zheng S, Yu JK, Hu X. Artificial neural networks analysis of surface‐enhanced laser desorption/ionization mass spectra of serum protein pattern distinguishes colorectal cancer from healthy population. Clin Cancer Res 2004;10:8380–8385. [DOI] [PubMed] [Google Scholar]
- 18. DeAngelis LM. Brain tumors. N Engl J Med 2001;344:114–123. [DOI] [PubMed] [Google Scholar]
- 19. Mannes AJ, Martin BM, Yang HY, et al. Cystatin C as a cerebrospinal fluid biomarker for pain in humans. Pain 2003;102:251–256. [DOI] [PubMed] [Google Scholar]
- 20. Yip TT, Chan JW, Cho WC, et al. Protein chip array profiling analysis in patients with severe acute respiratory syndrome identified serum amyloid a protein as a biomarker potentially useful in monitoring the extent of pneumonia. Clin Chem 2005;51:47–55. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Zelen M. Keynote address on biostatistics and data retrieval. Cancer Chemother Rep 1973;4:31–42. [PubMed] [Google Scholar]
- 22. Liu Y. Active learning with support vector machine applied to gene expression data for cancer classification. J Chem Inf Comput Sci 2004;44:1936–1941. [DOI] [PubMed] [Google Scholar]
- 23. Lin HH, Han LY, Cai CZ, Ji ZL, Chen YZ. Prediction of transporter family from protein sequence by support vector machine approach. Proteins 2006;62:218–231. [DOI] [PubMed] [Google Scholar]
- 24. Nelson DI, Concha‐Barrientos M, Driscoll T, et al. The global burden of selected occupational diseases and injury risks: methodology and summary. Am J Ind Med 2005;48:400–418. [DOI] [PubMed] [Google Scholar]
- 25. Seibert V, Wiesner A, Buschmann T, Meuer J. Surface‐enhanced laser desorption ionization time‐of‐flight mass spectrometry (SELDI TOF‐MS) and ProteinChip technology in proteomics research. Pathol Res Pract 2004;200:83–94. [DOI] [PubMed] [Google Scholar]
- 26. Somorjai RL, Dolenko B, Baumgartner R. Class prediction and discovery using gene microarray and proteomics mass spectroscopy data: curses, caveats, cautions. Bioinformatics 2003;19:1481–1491. [DOI] [PubMed] [Google Scholar]
- 27. Furey TS, Cristianini N, Duffy N, Bednarski DW, Schummer M, Haussler D. Support vector machine classification and validation of cancer tissue samples using microarray expression data. Bioinformatics 2000;16:906–914. [DOI] [PubMed] [Google Scholar]
- 28. Byvatov E, Schneider G. Support vector machine applications in bioinformatics. Appl Bioinformatics 2003;2:67–77. [PubMed] [Google Scholar]
- 29. Jorissen RN, Gilson MK. Virtual screening of molecular databases using a s support vector machine. J Chem Inf Model 2005;45:549–561. [DOI] [PubMed] [Google Scholar]
- 30. Wiesner A. Detection of tumor markers with proteinchip technology. Curr Pharm Biotechnol 2004;5:45–67. [DOI] [PubMed] [Google Scholar]
- 31. Liu Y, Sturgis CD, Grzybicki DM, et al. Microtubule‐associated protein‐2: a new sensitive and specific marker for pulmonary carcinoid tumor and small cell carcinoma. Mod Pathol 2001;14:880–885. [DOI] [PubMed] [Google Scholar]