Detection And Evaluation Of Serum Proteomic Patterns In Non-Small Cell Lung Cancer By SELDI-TOF-MS

OBJECTIVE: Up to now, the sensitivity and specificity of tumor biomarkers used in clinical practice are very low, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) is a new technique which can be used to detect albumen biomarkers of cancer patients,This study was to screen new biomarkers and build diagnostic models for diagnosis of non-small cell lung cancer by SELDI-TOF-MS,And investigate the clinical values of the models in diagnosis of lung cancer.METHODS :SELDI-TOF-MS was used to detect the serum proteomic patterns of lung cancer patients that have differential expression from age and sex-matched healthy people or Benign pulmonary lesions,The serum proteomic spectra were generated on weak cation exchange(WCX2) ,Differences in protein peaks were analyzed using Biomarker Wizard and SPSS 13.0 software,then build diagnostic models,and measure the tumor biomarkers of lung cancer patients at the same time,then compare the sensitivity between the diagnostic models and tumor biomarkers by statistic analysis,and research the diagnostic values of the models in lung cancer diagnosis.RESULT:A total of 13 protein peaks were detected by comparison 30 NSCLC with 30 healthy people (P<0.0001),and build a diagnostic model I of NSCLC which consisted of 3 protein peaks at 4797,2768,3268(m/z),and we proved that the the rate of accuracy of model I is 91.3%(158/173),and its sensitivity and specificity are 89.2%(66/74) and 92.9%(92/99),statistic analysis shows that it has a higher sensitivity than joint detection of CYF21 -1,SCC,CEA(P<0.001). A total of 7 protein peaks were detected by comparison 20 stage I NSCLC with 30 healthy people group(P<0.001), and build a diagnostic model II which composed by 3 protein peaks at 2768,3403,9498 (m/z), and we proved that the rate of accuracy of model II is 88%(40/50),and its sensitivity is 90%(18/20),Its specificity is 83.8 % (83/99) by the test of enlarged samples, statistic analysis shows that it has a higher sensitivity than joint detection of CYF21 -1,SCC,CEA(P<0.01).Comparing the 20 stage I NSCLC from the 11 Benign pulmonary lesions, 4 proteins with differential expression were discovered(p<0.05),we build a diagnostic model III which composed by 3 protein peaks at 1503,5928,25448 (m/z) further,we found that the rate of accuracy of model III is 93.5 % (29/31), and its sensitivity and specificity are 95% (19/20) and 90.9% (10/11). Comparing the 23 lung adenocarcinoma and 51 lung squamous cell carcinoma from 30 healthy people, the top 4 protein peaks at 3268, 2768, 3403, 9498 (m/z) were discovered,which be used to build diagnostic models IV,V,the models have high sensitivity and specificity for the diagnosis of lung adenocarcinoma or lung squamous cell carcinoma each, statistic analysis show that their sensitivities are higher than the tumor biomarkers which be related to the diseases. Comparing the 51 lung squamous cell carcinoma from the 23 lung adenocarcinoma, 4 protein peaks at 2955, 13751, 8565, 8697 (m/z) with differential expression were discovered(p<0.01),The AUC for the 4 biomarkers was ranged from 0.690-0.715.CONCLUSION: The diagnostic models I,II which composed by biomarker candidates screened by using SELDI-TOF-MS have high sensitivity and specificity for the diagnosis of NSCLC and stage I NSCLC patients,the sensitivity of the models are higher than the joint detection of tumor biomarkers;Diagnostic III is conducive to discriminate stage I NSCLC from Benign pulmonary lesions, especially for the patients which be suspicious of lung cancer by the X ray examination; Protein peaks at 3268,2768,3403,9498(m/z)have high sensitivity and specificity for the diagnosis of lung adenocarcinoma lung squamous cell carcinoma,there is hope to become new tumor biomarkers, apply to the diagnosis,valuation of curative effect and the survey of relapse after treatment. Protein peaks 2955, 13751, 8565, 8697 (m/z) ,If we can research their mechanism of action in occurrence and development of tumor,Maybe we can expound the differences in biological action or curative effect towards various treatments between lung squamous cell carcinoma and lung adenocarcinoma.