Abstract 1153: The development and utilization of a novel DNA microarray platform for biomarker and target identification in advanced prostate cancer
Steven M. WalkerCaroline McGoohanFionnuala A. McDyerGavin R. OliverNuala McCabeSteve DeharoPatrick G. JohnstonD. Paul HarkinRichard D. Kennedy
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Abstract Prostate cancer is the second leading cause of cancer-related deaths in men; specifically one in six men are diagnosed with prostate cancer in their lifetime. The use of serum prostate-specific antigen (PSA) levels has been lauded as a huge step forward in the diagnosis and treatment of prostate cancer, however since it's implemenatation as a biomarker it has become apparent that the numbers of deaths from prostate cancer has only decreased slightly. Therefore the identification of new biomarkers and treatments for highly invasive/metastatic prostate cancers is of a high priority. We sought to identify new biomarkers and drug targets by performing DNA microarray analysis of prostate tumour samples and normal prostate tissue samples. To further these goals we developed a specific array platform, this array was based upon extensive sequencing of prostate tumour samples and contains approximately 90,000 probesets many of which are specific to prostate cancer. We then utilized this technology to profile a series of fresh high Gleason score primary prostate tumour samples and normal prostate samples. We identified approximately 1,600 transcripts and many associated functionally relevant pathways that were significantly differentially expressed in the prostate tumour samples when compared with the normal prostate samples. Encouragingly we also identified several transcripts which are known to be specifically expressed in prostate cancer including prostate cancer antigen 3 (PCA3), α-methylacyl-coA-racemase AKA 2-methylacyl-CoA 2-epimerase (AMACR) and members of the olfactory receptor family 51, thereby demonstrating that this approach was producing reliable information. Additionally to these transcripts 34% of the 1,600 was annotated as being unique to the prostate cancer disease specific array when compared to available generic microarrays, thereby representing novel potential biomarkers and drug targets. Functional analysis of these unique transcripts annotated many to apoptotic processes, DNA repair and cellular proliferation amongst others. This content may be highly relevant to biomarker and target development for advanced prostate cancer. In conclusion we have developed a novel prostate cancer disease specific array, we have utilized this platform to profiled a series of prostate tumour and normal samples identifying several novel transcripts associated with advanced prostate cancer. Functional annotation of these unique transcripts associated many with processes know to be deregulated in cancer. We believe that this approach demonstrates the utility of this novel platform for the discovery of clinical biomarkers and novel drug targets from tumour tissue. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1153.Keywords:
Tissue microarray
Tissue microarray
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Objective To improve the dignosis and differential diagnosis of prostate adenovarcinoma. Methods Expression of prostate specific antigen(PSA)was detected by immunohistochemical methods in 199 benign prostate hyperplasia(BPH) and prostate adenocarcinoma tissues to understand indirectly the integrity of the basal cell layer. Results Expression of prostate specific antigen in most of prostate adenocarcinomas dewnre-hulated,but expression in benign prostate hyperplasia upregulated. Conclusions The study showed that PSA was a useful marker in the diagnosis and differential diagnosis of benign and malignant prostate lesions.
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Tissue microarray
TMPRSS2
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Objective To examine serum total Prostate Specific Antigen,f/t values and in identifying prostate Liang PSAD malignant diseases.Methods Select February,2008 to June,2009 the Group of Hospitals for treatment of 60 cases Prostate patients for the study of the random in A group(prostatic hyperplasia) 30 and B Group(prostate cancer) 30,the two patients the serum total Prostate Specific Antigen,free Prostate Specific Antigen and serum total Prostate Specific Antigen ratio(f/t) and prostate specific antigen density,testing and research.Results The study showed that A group serum total Prostate Specific Antigen is much lower than B Group f/t value exceeds B group,and prostate specific antigen density is much lower than the B Group,by comparison,P0.05 or P0.01,there are significant differences or very significant differences.Conclusion Prostate patients with malignant disease,Liang serum total Prostate Specific Antigen,f/t values and PSAD varies considerably,the identification of the higher value,it is worth further clinical applications.
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Percent free prostate specific antigen and prostate specific antigen density have been independently shown to increase the specificity of prostate cancer screening in men with prostate specific antigen levels between 4.1 and 10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent free prostate specific antigen and prostate volume on cancer detection in men with a prostate specific antigen between 2.6 and 10.0 ng/ml.From 1991 to 2005 all transrectal ultrasound guided prostate biopsies (5,587) for abnormal digital rectal examination and/or increased age specific prostate specific antigen were evaluated. A total of 1,072 patients with a prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free prostate specific antigen were included in study. The cancer detection rate was calculated for each percent free prostate specific antigen/volume stratum.Prostate cancer was detected in 296 patients (27.6%). The mean age and prostate specific antigen of the patients with benign pathology and prostate cancer were similar. Mean percent free prostate specific antigen was 17.5% and 14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively. The strongest risk factors for a positive biopsy were percent free prostate specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and digital rectal examination (OR 1.765, p=0.007), but not total prostate specific antigen (p=0.303). When stratified by volume and percent free prostate specific antigen, distinct risk groups were identified. The probability of detecting cancer inversely correlated with prostate volume and percent free prostate specific antigen.In men with prostate specific antigen levels between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely proportional to prostate volume and percent free prostate specific antigen. This table may assist in predicting patient risk for harboring prostate cancer.
Rectal examination
Prostate biopsy
Prostate cancer screening
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Objective To campare the expression of prostate stem cell antigen(PSCA) with that of prostate special antigen(PSA) in different prostatic tissues and the prostate adenocarcinoma tissues at different Gleason value levels.Methods Fifty-one cases of prostate adenocarcinoma,16 of prostatic intraepithelial neoplasms and 18 of benign prostatic hyperplasia were examined and analyzed by the SP immunohistochemical staining.Results There were significant differences of expressions of PSCA and PSA among prostate adenocarcinoma and prostate intraepifhelial and benign prostate hyerplasia(P0.05),however there was no difference between the expressions of the two antigens in prostate cancer tissues(P0.05).Conclusion It is possible for PSCA to become a new marker of the diagnosis of prostate adenocarcinoma in molecular pathology and a hot point of research.in the immunotheraphy of prostate adenocarcinoma.
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