Screen Hydrogaster Biomarkers With Relation To Hepatic Cirrhosis And Hepatocellar Carcinoma Research By Use Of SELDI Protein Chip Technology

Primary hepatic carcinoma (PHC) is the second cancer killer in China and accounts for 53 percent of all PHC deaths worldwide. Despite substantial progresses made in PHC clinical and basic research, the overall prognosis of PHC remains dismal because of the late diagnosis and low resection rate. Although alpha fetoprotein(AFP) remains the best PHC biomarker, the specificity and sensitivity of which are still not satisfied. Therefore, it is urgent to find out a simple technique of early diagnosis with high sensitivity and specificity at the clinical medical domain.With the completion of the human genome sequence project and the highly speed development of molecule biology, Science research experienced tremendous transformation from genome to proteome .The development of knowledge and technology in proteomics has provided a new way to diagnosis of the disease in the early stage .Surface enhanced laser desorption-ionization time of fight mass spectrometry (SELDI-TOF-MS) is one of the recently novel developed technologies, which to be able to analyse the complex biological sample powerfully. Render a strong and useful platform of research the occurrence and development of disease in proteomic. It has been already used in the early measuring and diagnosticing study of many kinds of diseases.Here we detect proteomes in hydrogaster from hepatic cirrhosis (LC) and PHC patients by use SELDI-TOF-MS and try to use software to identify proteomic difference between LC and PHC ,while decision tree classification algorithm of PHC were determined by Biomarker Patterns Software. Then we can screen the protein marker related PHC and find the proteomes configuration to diagnose the diseases of LC and PHC, which provide new clue and idea for the advancing study.Part one: Screening suitable protein chips for this research. Purpose: this part of research was to screen a suitable protein chip from two kinds of chips(CM10 and IMAC3) .Method: hydrogaster samples from 12 cases of LC patients and 12 cases of PHC patients were collected respectively, special protient or peptide spectra was determined by SELDI-TOF-MS measurement after treating the sample onto two kinds of protein chips for each case. According to the protein profiling results, we screen suitable protein chips.Result : in the scope of 2000-50000Da , CM10 chip detect 103 and 118 pieces of protein peaks from the group of LC and PHC, IMAC3 chip detect just only 53 and 57 pieces of protein peaks from the group of LC and PHC.Conclusion: CM10 chips can detect more significant difference protein peaks compared to IMAC3 chips and preferably apply to the research of the serum protein fingerprints.Part two: Screen hydrogaster biomarkers of LC and PHC, Establish the diagnostic patternsPurpose:Discover the proteins with relation to LC and PHC ,and provide new idea of finding the target of therapy and new biomarkers of LC and PHC, while establish diagnostic models of LC and PHC,investigate its feasibility of the clinical application.Method:Hydrogaster samples were collected from 30 cases of the LC and 30 cases of the PHC, the samples were profiled by SELDI-TOF-MS measurement using CM10 chips of ciphergen corporation, ciphergen biosystems software was used to analyze the proteomic profiles.Results:1. Comparison of the group of the LC and the group of PHC: analysis two groups of 59 samples and get 67 pieces of protein peaks, among them 24 pieces of protein peaks show the difference obviously in two groups compared ,16 proteins were up-regulated expression and 8 proteins were down-regulated expression in the PHC.2. Make use of those differenced proteins, 6 pieces of protein peaks are taken to establish a diagnostic cast by the software. Use this cast to measure the 59 unknown hydrogaster samples, the cast to estimate the result with double-blind test, accurate rate is 81.35%(48/59), sensitivity is 80.00% (24/30),specificity is 82.75% (24/29), positive predictive value is 82.75%(24/29), negative predictive value is 80.00%(24/30).Conclusion:1. There is significant difference among the group of the LC and the group of PHC in hydrogaster proteome, and those different proteins maybe the proteins related to the LC and the PHC. hepatic cell canceration maybe take place in the progress of hepatic cell regeneration. The progress possible relate with the 16 up-regulated expression proteins.2. The cast which established in this research can classify the patients of the LC and PHC.3. The technology of SELDI-TOF-MS and protein chip combined with bioinformatics software show great potential for the detection of the PHC and the LC in the clinical medicine .