Application of serum SELDI proteomic patterns in diagnosis of lung cancer.
BACKGROUND
Currently, no satisfactory biomarkers are available to screen for lung cancer. Surface-Enhanced Laser Desorption/ionization Time-of-Flight Mass Spectrometry ProteinChip system (SELDI-TOF-MS) is one of the currently used techniques to identify biomarkers for cancers. The aim of this study is to explore the application of serum SELDI proteomic patterns to distinguish lung cancer patients from healthy individuals.


METHODS
A total of 208 serum samples, including 158 lung cancer patients and 50 healthy individuals, were randomly divided into a training set (including 11 sera from patients with stages I/II lung cancer, 63 from patients with stages III/IV lung cancer and 20 from healthy controls) and a blinded test set (including 43 sera from patients with stages I/II lung cancer, 41 from patients with stages III/IV lung cancer and 30 from healthy controls). All samples were analyzed by SELDI technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peaks clustering and classification analyses were made using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. We additionally determined Cyfra21-1 and NSE in the 208 serum samples included in this study using an electrochemiluminescent immunoassay.


RESULTS
Five protein peaks at 11493, 6429, 8245, 5335 and 2538 Da were automatically chosen as a biomarker pattern in the training set. When the SELDI marker pattern was tested with the blinded test set, it yielded a sensitivity of 86.9%, a specificity of 80.0% and a positive predictive value of 92.4%. The sensitivities provided by Cyfra21-1 and NSE used individually or in combination were significantly lower than that of the SELDI marker pattern (P < 0.005 or 0.05, respectively). Based on the results of the test set, we found that the SELDI marker pattern showed a sensitivity of 91.4% in the detection of non-small cell lung cancers (NSCLC), which was significantly higher than that in the detection of small cell lung cancers (P < 0.05); The pattern also had a sensitivity of 79.1% in the detection of lung cancers in stages I/II.


CONCLUSIONS
These results suggest that serum SELDI protein profiling can distinguish lung cancer patients, especially NSCLC patients, from normal subjects with relatively high sensitivity and specificity, and the SELDI-TOF-MS is a potential tool for the screening of lung cancer.
Yang
Shuan-ying
SY
Department of Respiratory Medicine, Second Hospital of Xi'an Jiaotong University, Xi'an, 710004, China. yangshuanying@21cn.com
Xiao
Xue-yuan
XY
Zhang
Wang-gang
WG
Zhang
Li-juan
LJ
Zhang
Wei
W
Zhou
Bin
B
Chen
Guoan
G
He
Da-cheng
DC
D000328:Adult; D000368:Aged; D000465:Algorithms; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism; D002412:Cations; D003663:Decision Trees; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007118:Immunoassay; D053539:Keratin-19; D007633:Keratins / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002412:Cations; D053539:Keratin-19; C102012:antigen CYFRA21.1; D007633:Keratins