Study On Differential Proteins Of Bronchogenic Carcinoma By SELDI-TOF-MS

Objectives To research the differential proteins in sera,bronchoalveolar lavage fluid(BALF) and lung tissue in patients with lung cancer and benign lung disease by surface-enhanced laser desorption ionization time of flight mass spectrometry(SELDI-TOF-MS) technology and identify the relationship between proteins and lung cancer and their significance.Methods Application of SELDI-TOF-MS technology,protein chips weak cation exchange(WCX-2 chips) were used to evaluate the differences of protein in sera,BALF and lung tissue in patients with lung cancer(20 cases) or benign diseases(10 cases),And the Protein Chip Biomarker SystemⅡ-C-protein chip instrument was used to read the chip information.The software of Ciphergen protein chip 3.2 version was used automatically to collect the data,read the peak height values,and access the expression profile of protein for statistical treatment. The data read by Biomarker Pattern Software was analyzed to find differentiated protein of NSCLC and set up the initial model of diagnosis,and verify the diagnosis through blind screening model.Results The protein differences in patients with lung cancer or benign lesions were as followed:(1) Sera:20 of protein peaks have been found significant difference in patient with lung cancer.Among them,14 protein peaks were significantly higher expression(P<0.05),their M/Z were separately 3270.07Da, 4095.44Da,5309.20Da,5340.15Da,5852.02Da,5906.89Da,6436.01Da,6632.41Da, 6933.33Da,7768.18Da,7973.40Da,8065.61Da,8691.12Da and 8142.28Da;there were six peaks significantly lower expression of the protein(P<0.05),their M/Z were separately 2014.68Da,2137.45Da,2280.16Da,2503.32Da,3588.92Da and 2090.78Da;By using Biomarker Pattern Software(BPS) on the analysis of the data obtained by processing,The differential proteins whose M/Z were 2090.77 Da and 2503.31Da were established classification tree model,it s diagnostic sensitivity is 90%and specificity was 100%.The results verified by blind screening showed a sensitivity of 90%and specificity of 100%,crude accuracy(CA) of 93.33%and Youdens index(γ)of 0.9.(2) BALF:it was found that there is significant difference among the 18 protein peaks,four peaks of high expression protein in BALF of patients with lung cancer,the M/Z were 7280.59 Da,7766.12Da,7824.82 Da and 11510.51 Da;there also were 14 peaks in lower expressed protein(P <0.05),the M/Z were separately 2368.58Da,2382.53Da,2618.62Da,3377.17Da,3448.29Da, 3494.11Da,3512.82Da,4140.77Da,4996.49Da,5426.08Da,6925.46Da,10837.31Da, 13160.91Da,12691.68Da.The differential proteins whose M/Z were 2611.61Da and 3252.80Da were established classification tree model,it s diagnostic sensitivity was of 100%and specificity was of 100%.The results verified by blind screening showed a sensitivity of 90%and specificity of 100%,CA of 96.67%andγof 0.97.(3) lung tissue homogenate:it was found 11 significant difference protein peaks in patients with lung cancer,three peaks of high expression protein in lung tissue homogenate of patients with lung cancer,the M/Z were separately 4230.06Da,5757.93Da and 11497.18Da;there were eight peaks lower expression of the protein(P<0.05),their M/Z were separately 2301.92Da,2315.62Da,2331.54Da, 2488.96Da,3507.10Da,3525.91Da,4770.84Da and 4742.71Da.The differential proteins whose M/Z were 5757.92Da and 4742.71 Da were established the classification tree model for the diagnosis of lung cancer,it s diagnostic sensitivity was of 100%and specificity was of 100%,CA of 93.33%andγof 0.9.The results verified by blind screening showed a sensitivity of 90%and specificity of 100%. The blind screening trial mentioned above were tested by parallel test,20 of 30 cases patients were sentenced to lung cancer patients,10 of them to benign pulmonary diseases ones winthout any wrong judgement according to the pathological results.Conclusions(1) The relatively specific protein markers selected by SELDI-TOF-MS technology were more sensitive and specific for diagnosis of lung cancer.(2) Patients with lung cancer and benign pulmonary lesions in patients with the existence of statistical differences in 20 protein peaks,BALF there exists significant difference between the 18 protein peaks,the existence of tissue homogenate 11 are significantly different protein peaks.These proteins may be related to the biological characteristics of lung cancer.(3) If anyone positive result of the detection of three specimens mentioned above by SELDI-TOF-MS was applied to diagnose lung cancer,the sensitivity and specificity of diagnosis of lung cancer would be of 100%.