| Objective: To analyze the differential expression of serum proteins mass spectra among chronic hepatitis B,liver cirrhosis after hepatitis B, hepatocellular carcinoma related with HBV and healthy controls and establish a diagnosis model.Compare the differential expressive proteins among hepatitis,liver cirrhosis and hepatocellular carcinoma with a view to look for the specific protein peak related to the differential diagnosis,to determine the stage of hepatopathy development and reveal the occurrence and developing law of liver cancer.Methods: Using surface enhanced laser desorption ionization time of flight mass spectrometry technology (SELDI-TOF-MS)and weak cation chip CM10 to analyze mass spectra of serum samples including 60 cases of chronic hepatitis B , 42 cases of liver cirrhosis, 79 cases of hepatocellular carcinoma and 56 cases of healthy controls. Biomarker Pattern Software (BPS) was used to detect the protein peaks significantly different among them and establish a diagnostic pattern which was further valuated by a blind test to verify the accuracy of diagnosis and differential diagnosis.Results: 9 significantly different protein peaks were found in serum samples between 60 chronic hepatitis B patients and 56 healthy controls. Protein peaks were 2736Da,2753Da,4101Da,4206Da,4310Da,6447Da,6642Da,15132Da,15897 Da. BPS choose 2736Da to build up a taxonomic tree model(model I) which can correctly divide hepatitis and healthy controls of 100%. The sensitivity,specificity , positive predictive value,negative predictive value of blind test of 51 cases was 91.30%,89.28%,87.50%,92.59%. 8 significantly different protein peaks were found in serum samples between 42 liver cirrhosis and 56 healthy controls. Protein peaks were 2736Da,2753Da,4101Da,6447Da,6642Da,9337 Da,15132Da,15897 Da. BPS choose 2736Da to build up a taxonomic tree model(modelâ…¡) which can correctly divide cirrhosis and healthy controls of 100%. The blind screen of 28 serum samples has the sensitivity and specificity of 100%.8 significantly different protein peaks were found in serum samples between 79 HCC patiens and 56 healthy controls. Protein peaks were 2753Da,3401Da,4101Da,5641Da,6447Da,6642Da,7807Da,9337 Da. BPS choose 3401Da,4101Da,5641Da to build up a taxonomic tree model(modelâ…¢) which can classify 89.65% of HCC patients and 92.68% of healthy controls. The sensitivity,specificity , positive predictive value, negative predictive value of blind test of 51 cases was 90.47%,81.25%,86.36%,86.67%. Compared with liver cirrhosis, peak values of 3401Da,9210Da,9337Da up-regulated in hepatitis patients. 10 protein peaks were significantly different between hepatitis and HCC patients,a differential diagnosis model (modelâ…£)between them was set up consisting of 3 protein peaks with M/Z values of 2736Da,2753Da,3401Da which can classify 100% hepatitis and 98.04% of HCC patients.Blind test of 49 cases confirmed a sensitivity of 90.91%,specificity of 85.71%,positive predictive value of 71.42%,negative predictive value of 96.00% respectively. 11 protein peaks were significantly different between liver cirrhosis and HCC patients,a differential diagnosis model (modelâ…¤)between them was set up consisting of 3 protein peaks with M/Z values of 2753Da,9337Da,15132Da which can classify 88.09% cirrhosis and 86.00% of HCC patients. Blind test of 50 cases confirmed a sensitivity of 76.19%,specificity of 72.41%,positive predictive value of 66.67%,negative predictive value of 80.77% respectively.Conclusion: Significantly different protein peaks can be screened out in chronic hepatitis B,liver cirrhosis after hepatitis B,HBV-related HCC and healthy controls using SELDI-TOF-MS technology. Protein peaks with M/Z values of 2736Da,15132Da,15897Da may be specific to benign liver diseases. Four Protein peaks with M/Z values of 3401Da,5641Da,7807Da,9337Da may be the identification of HCC and non-HCC and change of Protein peak 5641Da may predict the degree of progress of liver diseases. Change of protein peak 4101Da may indicate the occurrence of liver diseases. Protein peaks with M/Z values of 2753Da,6447Da,6642Da may be the serum markers to identify HCC,benign liver diseases and healthy controls. The sensitivity,specificity and accuracy of diagnostic model is high which has certain significance in diagnosis,identification and screening of specific biological markers for HCC and its related liver diseases. |
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