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Identification Of Candidate Prostate Cancer Biomarkers In Prostate Needle Biopsy Specimens Using Proteomic Analysis

Posted on:2009-05-13Degree:MasterType:Thesis
Country:ChinaCandidate:J XuFull Text:PDF
GTID:2144360272459855Subject:Surgery
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Objective:To observe the clinical significance of AMACR (α- methylacyl - CoA racemase ) and quest for new diagnosis methods for prostate cancer.METHODS:108 prostate needle biopsies were used to detect prostate cancer on immunohistochemical method forα- methylacyl - CoA racemase.Among these cases,24 biopsies were taken from 24 cases each for Western blot.All tests were done with double blind method.RESULTS:On immunohistochemical methods,the positivity was 96.7%comparing with the last diagnosis. Among 61 negative cases,2 cases were false positive,the positivity was 93.2%.In 44 cases of Adenocarcinomas,3 cases were missed diagnosis,the positivity was 93.2%.One case of prostate small cell carcinoma showed positive staining.One case of metastatic prostate cancer showed negative staining,and one case of HPIN weak positive. On Western blot,the positivity was 87.5%.Among 14 negative cases, no case were false positive.The positivity was 100%.In 10 positive cases,3 were missed diagnosis.The positivity was 70%.The results of Western blot showed clear bands and definite patterns between positive and negative cases.Micro foci of prostate cancers could be found when using immunohistochemistry for AMACR.CONCLUSIONS: AMACR is a useful new biomarker for prostate cancer diagnosis. AMACR detected by immunohistochemistry and Western blot can help the diagnosis for prostate cancer.It will keep foreground for further research. Although serum prostate specific antigen(PSA) is a well-established diagnostic tool for prostate cancer(PCa) detection,the definitive diagnosis of PCa is based on the information contained in prostate needle biopsy(PNBX) specimens.To define the proteomic features of PNBX specimens to identify candidate biomarkers for PCa,PNBX specimens from patients with PCa or benign prostatic hyperplasia(BPH) were subjected to comparative proteomic analysis. 2-DE revealed that 52 protein spots exhibited statistically significantly changes among PCa and BPH groups.Interesting spots were identified by MALDI-TOF-MS/MS.The 2 most notable groups of proteins identified included latent androgen receptor coregulators[FLNA(7-15) and FKBP4]and enzymes involved in mitochondrial fatty acid b-oxidation(DCI and ECHS1).An imbalance in the expression of peroxiredoxin subtypes was noted in PCa specimens.Furthermore,different post-translationally modified isoforms of HSP27 and HSP70.1 were identified.Importantly, changes in FLNA(7-15),FKBP4,and PRDX4 expression were confirmed by immunoblot analyses.Our results suggest that a proteomics-based approach is useful for developing a more complete picture of the protein profile of PNBX specimen.The proteins identified by this approach may be useful molecular targets for PCa diagnostics and therapeutics.
Keywords/Search Tags:prostate cancer, AMACR (α-methylacyl-CoA racemase), Western blot, immunohistochemstry, prostate needle biopsy, 2-DE, mass spectrometry, needle biopsy, prostate cancer
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